An mRNA Vaccine that Works

By KLG, who has held research and academic positions in three US medical schools since 1995 and is currently Professor of Biochemistry and Associate Dean. He has performed and directed research on protein structure, function, and evolution; cell adhesion and motility; the mechanism of viral fusion proteins; and assembly of the vertebrate heart. He has served on national review panels of both public and private funding agencies, and his research and that of his students has been funded by the American Heart Association, American Cancer Society, and National Institutes of Health.

Although pancreatic ductal adenocarcinoma (PDAC) is relatively uncommon with about 60,000 cases per year in the United States, it is expected to be the second leading cause of cancer-related mortality by 2030 (current cancer statistics).  Of all the cancer diagnoses, PDAC may rival glioblastoma as one of the most dreaded.  Both appear “out of the blue” so to speak.  In contrast, 90% of lung cancer patients have a well-known risk factor that is a matter of personal choice, granted followed by addiction.  While glioblastoma is essentially a terminal diagnosis, PDAC does not lag far behind.  In 2020 the 5-year survival rate [1] for PDAC was 5%.  By 2020 this had risen to nearly 10%.  Although 5-year survival can be a useful metric, in the case of PDAC most of this increase has been due to improved clinical management of the disease using multiagent cytotoxic therapies, primarily in the form of FOLFIRINOX.  This cocktail includes flurouracil, irinotecan, leucovorin, and oxaliplatin and is frankly scary.  The side effects will be severe for many patients, with the ultimate outcome predetermined.

Surgery is the only “cure” for PDAC but is possible in relatively few cases, largely because this cancer is not often diagnosed until it is advanced and frequently metastatic.  Earlier this year I was tutoring a group of medical students when the subject of pancreatic cancer surgery came up.  We went to the online three-dimensional anatomy resources, and one look illustrates why a good surgeon cannot simply “cut PDAC out.” (Figure 1) There is way too much going on around the head of the pancreas, involving the superior mesenteric artery and superior mesenteric vein, for a surgeon to be able to intervene without killing the patient. Any successful treatment of PDAC will require a different approach.

And this brings us to the topic for today: Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer, which was published online in Nature on 10 May 2023.  The conclusion from this report is that this mRNA vaccine works in a proof-of-principle study.  Highlights of this current paper will be covered below, but a deeper understanding of how a novel mRNA cancer vaccine was developed is required for a full appreciation of why this research has such great potential.

Although PDAC usually kills relatively quickly, long-term survivors exist, and this has been attributed to T cell-mediated immunity in these patients.  This research team previously published Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer (November 2017), which supports this observation.  A cascade of mutations is the hallmark of cancer development and progression, and neoantigens are novel protein products of mutant genes in transformed/cancer cells.  They appear both early and late during cancer progression, which is usually a long, multistep process.  If they are recognized as non-self, they can become targets of the immune system.

In this very detailed paper, Vinod P. Balachandran of Memorial Sloan Kettering Cancer Center (MSKCC) in New York and a large international team [2] took a multidisciplinary approach to identify T-cell antigens in long-term PDAC survivors.  They found that “tumors with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates (indicative of an immune response to the tumor), but neither alone, stratified patients with the longest survival.”  Moreover, neoantigens were found in MUC16, which is also known as CA125.  Cancer Antigen 125 was identified more than 40 years ago as characteristic of ovarian and many other cancers and is used frequently as a clinical marker of cancer.  It is a cell surface glycoprotein (a membrane protein exposed on the outer surface of the cell with sugars attached to it) and therefore readily “visible” to the immune system.

A primary result of this study is that long-term survivors of PDAC [median survival of 6 years (n = 82) versus 0.8 years (n = 68)] mounted the best immune response to the neoantigens.  The survival curves in Figure 1 and Figure 2 of this paper are convincing.  And notably, this research “observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting (more on this below).”   Thus, this research published in 2017 identified high-potential markers that can be targets for immune therapy specific for PDAC and showed that the loss of these neoantigens correlates with PDAC progression/metastasis.

The theory proposed by Macfarlane Burnet [3] that immunosurveillance “eliminates transformed cells (i.e., cancer cells) as an evolutionary necessity to maintain tissue homeostasis” goes back to the 1950s.  Otherwise, spontaneous mutations that lead inexorably to tumors would win.  As noted subsequently in Neoantigen quality predicts immunoediting in survivors of pancreatic cancer (May 2022):

“This theory of ‘cancer immunosurveillance was later redefined more broadly as ‘cancer immunoediting’ – as a consequence of the immune system protecting the host from cancer, the immune system must also sculpt developing cancers.  When cancers develop, they accumulate mutations, some of which generate new protein sequences (neoantigens). As neoantigens are mostly absent from the human proteome, they can escape T cell central tolerance in the thymus to become antigens in cancers. However, neoantigens typically arise in passenger mutations, and therefore distribute heterogeneously in cancer cell clones with variable immunogenicity. Thus, T cells selectively ‘edit’ clones with more immunogenic neoantigens, inducing less immunogenic clones to outgrow in cancers.”

This is complicated for the non-immunologist (me) and the layperson, but the theory is that immunoediting allows the immune system to kill the more immunogenic cancer cells and this can lead to less immunogenic clones, i.e., cancer cells that are less susceptible to attack by the immune system, to predominate in the population of cancer cells of a tumor.  This has been proven in mice but has remained unclear in humans.  To address this question, the evolution of 70 human PDAC tumors over 10 years was studied.  The result is that “despite having more time to accumulate mutations, rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumors develop genetically less heterogeneous recurrent tumors with fewer immunogenic mutations (neoantigens).”  The conclusion reached after extensive experimental and theoretical analysis is that the human “immune system fundamentally surveils host genetic changes to suppress cancer.” Macfarlane Burnet was correct as expected, and as he had to be.

Which leads us back to the current paper from this research group: Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer (May 2023).  Their previous research showed that cells in PDAC express cancer-specific neoantigens that are suitable for the development of cancer vaccines.  An mRNA vaccine was developed to test this hypothesis.  The techniques used are sophisticated, but they are not experimental, in that any well-supported molecular biology laboratory could do this work.  This is also why the COVID-19 mRNA vaccines were feasible in principle and were developed so rapidly before and during Operation Warp Speed.

The novel part of the research described here is that the mRNA neoantigen vaccines were “synthesized in real time from surgically resected PDAC tumors” from individual patients.  Sixteen (16) patients were treated with this autogene cevumeran mRNA vaccine and the immune checkpoint inhibitor atezolizumab [4] and then 15 of these 16 patients were treated with conventional FOLFIRINOX adjuvant chemotherapy.  Figure 1 is a composite describing the trial design.  This figure is complicated, but the results show that the protocol is both feasible and safe.  Well-chosen clinical endpoints included vaccine-induced neoantigen-specific T cells and 18-month recurrence-free survival (RFS).  Half (8 of 16) of the patients receiving the vaccine induced high levels of neoantigen T cells, which indicates that the immune response to the tumor neoantigens was robust in half of the trial participants.

The key finding in this study is that subjects who mounted an immune response to the neoantigens showed a longer period of recurrence-free survival (Figure 3).  Figure 3a shows the responses (OS, overall survival) and RFS in the safety-evaluable cohort.  Figure 3b illustrates the primary result.  Median RFS was not reached in either time from surgery or time from landmark (date of the last vaccine priming dose) as shown by the red survival curves.  Median RFS for the non-responders was 13.4 months from surgery and 11.0 months from landmark (blue survival curve).  These results demonstrate that the mRNA vaccines to PDAC are effective when the neoantigens induce an immune response, which they did in 50% of the patients in the first test of this experimental and clinical approach to PDAC.

Perhaps just as importantly, the vaccine may be effective against metastatic PDAC, which is incurable by surgery and eventually fatal.  Directly from the paper (Figure 4; the links in this excerpt are functional in manuscript; I have followed each of them and they support the reported results based on my understanding of the experimental rationale and techniques used):

“Patient 29 responded to autogene cevumeran with the second-highest maximal percentage of expanded blood T cells (Fig. 2b) that included vaccine neoantigen-specific polyfunctional CD8+ T cells…Patient 29 developed increased serum CA19-9 (a marker of pancreatic cancer somewhat analogous to MUC16/CA125) levels with a new 7-mm liver lesion suggestive of a metastasis after vaccine priming (Fig. 4a).  A biopsy sample did not reveal malignant cells but a dense lymphoid infiltrate (Fig. 4b, left) that included all 15 autogene-cevumeran-expanded (Fig. 4b, middle) CD8+ T cell clones with phenotypic evidence of lytic and effector potential (Fig. 4d) (i.e., immune cells that can kill cancer cells).  Digital droplet PCR revealed that this lymphoid infiltrate contained rare cells harboring the TP53R175H mutation, identical to the R175H (the amino acid arginine replaced by the amino acid histidine at position 175 in the protein TP53, previously called p53) driver mutation in the primary tumor of this patient (TP53 mutants that affect DNA repair are common in cancer cells)…This liver lesion disappeared on subsequent imaging (Fig. 4a), which suggests that autogene-cevumeran-expanded T cells may possess the capacity to eradicate micrometastases.”

Yes, this is only one patient, but this could be the one patient that allows the research to be extended to the treatment of metastatic PDAC, and perhaps other cancers for which this mRNA vaccine strategy may be useful.

The title of this post is “An mRNA Vaccine that Works.”  Do the results reported here support that conclusion? Yes, in my view they do.  The number of patients enrolled it the trial was necessarily small, but the outcomes are clear.  Those patients who mounted an immune response to the vaccines had longer recurrence-free survival times than those whose immune response was minimal.  Moreover, in one patient who developed a pancreatic cancer metastasis after the beginning of the trial eliminated the metastasis.

Is this approach feasible at scale?  That depends on the scale.  60,000 PDAC patients per year is a large number.  But the foundation for continued success is strong, especially given the resources available at MSKCC and at other similar cancer research institutions/hospitals.  Expensive?  Yes, but that will also depend on the future of our healthcare system (few reasons for hope on that horizon).  Generalizable to other cancers?  Probably.  The “holy grail” of cancer therapy has always been to find an intervention that kills the cancer while sparing the host, who would be you and me.  So far, the best we can do much of the time is kill cancer cells faster than we kill healthy cells.  Surgery, when possible, plus chemotherapy and radiation oncology often work very well, and these interventions have been a triumph of clinical oncology.

Regarding a “magic bullet” for cancer, one of my tasks in the laboratory a long time ago was to purify ricin from castor beans, which would then be conjugated to antibodies that recognize specific cancer cells.  This antibody-ricin conjugate would be taken up by these cells and the passenger ricin would then kill them [5].  I have not looked lately, but this particular approach did not seem likely to work.  Prostate brachytherapy (insertion of radioactive pellets) has been useful in the treatment of prostate cancer and is a nearly literal magic bullet of another sort that kills cancer cells in the tumor while not affecting surrounding areas.

A current directed approach to cancer is CAR T-cell therapy (CAR: chimeric antibody receptor) for various leukemias and lymphomas.  This is very promising but difficult and extremely labor intensive and expensive as described at the link:

“Currently available CAR T-cell therapies are customized for each individual patient. They are made by collecting T cells from the patient and re-engineering them in the laboratory to produce proteins on their surface called chimeric antigen receptors, or CARs. The CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells… After the revamped T cells are “expanded” into the millions in the laboratory, they’re then infused back into the patient. If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”

The cellular and molecular mechanisms of CAR T-cell therapy are similar to those of the PDAC vaccines described here.  The mRNA vaccine approach seems more direct and more likely to work for solid tumors.  And mRNAs tunable to an individual cancer in real time.  It is important to remember that cancer is a thousand different diseases, and each individual cancer consists of a genetically heterogenous population of cells that are most likely derived from one progenitor mutant cell.  As shown in the research described here, the PDAC vaccine can be prepared from an individual tumor in real time and used in a matter of days as personalized therapy.  In this first study, only 50 percent of the patients mounted the necessary immune response.  Further research should identify the reasons for this.  But if even if the exact mechanisms are never known, which has been true for sometimes successful immune approaches to cancer that have preceded CAR T-cell therapy, a 50% success rate based on well understood underlying biology is a strong result.

Nevertheless, mRNA vaccines have had a checkered past and present, even though an mRNA vaccine has been more or less obvious since Francis Crick proposed the Central Dogma of Molecular Biology in the late-1950s: DNA makes RNA makes Protein.  With an mRNA vaccine the protein produced in host cells is the antigenic component of the vaccine.  However, mRNA vaccines against Zika virus are still a work in progress, to my knowledge.  The mRNA vaccines against SARS-CoV-2/COVID-19 have not met expectations, which were probably unreasonable for a respiratory virus.  Plus, it has long been known that lasting immunity to coronaviruses has been difficult to induce by vaccines or to sustain after infection.  That may eventually change.  In the meantime, COVID-19 is still here.

Which brings us to a final point about immune surveillance and the maintenance of tissue homeostasis in animals, meaning us, that helps keep us mostly cancer-free.  The work described here has shown that our immune system can identify pancreatic cancer cells and kill them.  A well-known cancer antigen (MUC16/CA125) is a prominent target neoantigen in PDAC.  After showing that immune surveillance is involved in the development of PDAC, the mRNA vaccine followed.  Half of the patients who received the vaccine mounted an effective response to PDAC, including perhaps to a liver metastasis.  This is remarkable in every good way, an example of good science done well, and while the effort was large this science is not the “Big Science” that Karl Popper rightly feared would eclipse good science.  Nor is it typical of what has become evidence-based medicine.

One of the worries about COVID-19 is that immune system dysregulation that seems to follow SARS-CoV-2 infection in many pandemic survivors will lead to impaired immune surveillance in these individuals.  Will a cancer epidemic follow the COVID-19 pandemic as immune surveillance in COVID-19 survivors is attenuated?  This is a good question, one that has been asked here from time to time.  The answer is currently unknown.  In the meantime, go long on masks and encourage good behavior when and where necessary.  Other non-pharmaceutical interventions (NPI) such as air filtration and improved ventilation are engineering solutions that work.  Also trust that scientists out there are following David Ho and others, who introduced the triple therapy that rendered AIDS a manageable chronic condition that is symptom-free among many of those infected with HIV.  Since coronaviruses may be persistent but do not insert themselves into the host genome, antiviral compounds for COVID-19 seem to be a likely solution to the pandemic, along with broadly active intranasal vaccines that interfere with initial infection.

But regarding pancreatic cancer, an mRNA vaccine has shown great promise.  The RNA World has been a thing for the past 30 years.  Now RNA therapeutics are beginning to show their utility along with proteins (e.g., atezolizumab and trastuzumab).  We need only vision and resolve to make them work in the wider clinical world.


[1]  Many years ago, a measurable increase in 5-year survival rate for lung cancer was trumpeted as a success story by the Cancer Establishment.  I was initially very hopeful, given that my father had been a smoker since the US Navy taught him the habit as a 19-year-old in 1949, and he had been a chemical worker since leaving the Navy in 1953.  Thus, his risk factors were considerable.  It turns out that when the data were analyzed further, most of the 5-year survivors eventually died of lung cancer anyway, and the increase in survival rate was an artifact if improved clinical management.  My father died of a brainstem tumor secondary to lung cancer five weeks after his 55th birthday.

[2]  This research was supervised jointly by Taha Merghoub and Steven D. Leach, with MSKCC and other relevant affiliations.  Following the current necessary convention, “competing financial interests” are available in the online version of the paper at the link.  For what it’s worth, the list seems shorter than usual.  In my view the data presented are very strong, without the necessity of statistical reasoning to make their argument.  Statistical significance here seems very correlated with clinical relevance, which is not a given in modern “evidence-based medicine.  This is true of all the primary research covered here.

[3]  And others.  Throughout the middle of the 20th century the discipline of immunology was developed by a large group if biologists and physicians.  It is still very much a work in progress.

[4]  From the National Cancer Institute link: Atezolizumab is a type of targeted therapy drug called an immune checkpoint inhibitor. It is a monoclonal antibody that works by binding to the protein PD-L1 on the surface of some cancer cells, which keeps cancer cells from suppressing the immune system. This allows the immune system to attack the cancer cells.

[5]  Ricin is justifiably infamous.  One molecule is probably enough to kill one cell, and the poison was the agent used to assassinate the Bulgarian dissident Georgi Markov in London in 1978.  But ricin is poisonous only when injected, although consumption of castor beans is not recommended.  Ricin, which is also a lectin (carbohydrate binding protein) is not soluble in oil, so castor oil is not dangerous, for this particular reason.

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About Lambert Strether

Readers, I have had a correspondent characterize my views as realistic cynical. Let me briefly explain them. I believe in universal programs that provide concrete material benefits, especially to the working class. Medicare for All is the prime example, but tuition-free college and a Post Office Bank also fall under this heading. So do a Jobs Guarantee and a Debt Jubilee. Clearly, neither liberal Democrats nor conservative Republicans can deliver on such programs, because the two are different flavors of neoliberalism (“Because markets”). I don’t much care about the “ism” that delivers the benefits, although whichever one does have to put common humanity first, as opposed to markets. Could be a second FDR saving capitalism, democratic socialism leashing and collaring it, or communism razing it. I don’t much care, as long as the benefits are delivered. To me, the key issue — and this is why Medicare for All is always first with me — is the tens of thousands of excess “deaths from despair,” as described by the Case-Deaton study, and other recent studies. That enormous body count makes Medicare for All, at the very least, a moral and strategic imperative. And that level of suffering and organic damage makes the concerns of identity politics — even the worthy fight to help the refugees Bush, Obama, and Clinton’s wars created — bright shiny objects by comparison. Hence my frustration with the news flow — currently in my view the swirling intersection of two, separate Shock Doctrine campaigns, one by the Administration, and the other by out-of-power liberals and their allies in the State and in the press — a news flow that constantly forces me to focus on matters that I regard as of secondary importance to the excess deaths. What kind of political economy is it that halts or even reverses the increases in life expectancy that civilized societies have achieved? I am also very hopeful that the continuing destruction of both party establishments will open the space for voices supporting programs similar to those I have listed; let’s call such voices “the left.” Volatility creates opportunity, especially if the Democrat establishment, which puts markets first and opposes all such programs, isn’t allowed to get back into the saddle. Eyes on the prize! I love the tactical level, and secretly love even the horse race, since I’ve been blogging about it daily for fourteen years, but everything I write has this perspective at the back of it.


  1. Amfortas the hippie

    this is excellent, KLG.
    when Wife was first diagnosed(stge 4 colon cancer, K-ras, already the size of a volleyball), i went nuts with a research frenzy, trawling pubmed, etc to both get my mind around what, exactly, was happening within her…as well as to maybe notice some treatment option that had been overlooked…since the experts to hand(who were all top notch, imo) were so busy with their work that they hadn’t the time to do any outside of box thinking.
    MRNA cancer vaccines were one of the things i came across…i knew immediately and intuitively that this tech could revolutionise cancer treatment…if they could get it to work.
    that last part had been the problem, of course,lol.
    given her prognosis, i wasnt worried all that much about induced autoimmune problems and the like…the derned tumor was the immediate problem to be solved.
    but the autoimmune issues, and similar problems, had put research into this tech on the back burner, overall…they hadnt really even begun trying to apply it to colorectal cancers.
    i dont think it would have helped my Wife that much anyway….her cancer was too far advanced by the time of diagnosis(tumor began on the outside of the colon, thus no blockage, thus no symptoms until it had grown very large).
    and i also had little hope for applying it to covid, given the high mutation and immune evasion of the whole zoo of coronaviruses(turned quickly into a magic bullet profit center at the expense of NPI, Nasal, etc)
    but for cancer, in general, i still think that this tech has real promise.
    it remains the only cancer related science thing i actually go and read when i come across a study, somewhere.-

  2. tindrum

    The mRNA train jst keeps rollin’ down the track it would seem.
    One major problem is the dosing – no one can predict where the RNA goes, how much RNA actually reaches the cells, wherever they may be, and how much protein they then produce, so no one knows how much to put in the shot, is this maybe an issue?
    Also given the parlous state of vaccine testing in the USA I would nto trust this study as far as I could throw its authors.

    I quote here from the book ‘Turtles all the way down: Vaccine Science and Myth’

    “Vaccine manufacturers and health authorities worldwide frequently assure us, the public, that vaccines are tested at the highest possible level and that the rigorous series of clinical trials they undergo as part of the licensing process ensures that vaccines are truly safe and effective. These assurances, however, are meaningless at best and deliberately misleading at worst. As we have seen in this chapter, vaccine trials are designed and performed in such a way as to ensure that the true extent of adverse events is hidden from the public.

    There is not a single vaccine in the US routine childhood vaccination program whose true rate of adverse events is known. ”

    Anonymous. Turtles All The Way Down: Vaccine Science and Myth (p. 81). The Turtles Team. Kindle Edition.

    1. Oz

      There is a whole discipline of pharmacokinetics which measures where drugs go in the body, how long they stick around, how they’re metabolized, and how they’re excreted. It’s not an ‘unknown’ simply because it’s unknown to you.

      1. Jeremy Grimm

        Knowing that “there is a whole discipline of pharmacokinetics which measures where drugs go in the body, how long they stick around, how they’re metabolized, and how they’re excreted” — is of little comfort — in and of itself. How often is this discipline applied? Are pharmacokinetic studies a part of the standard drug development protocols?

        There are many things I do not know, but there are also many things I am not told and for which finding a reliable answer is at best occult to a layman like me. But not knowing is not the same as being incapable of knowing or indolent in seeking out knowledge — which I hope was not an intent of your comment. Recent experiences with the Corona pandemic has greatly undercut the expert’s happy talk claim that we should just trust that the experts ‘have this’.

        1. bioengineer

          Dont die on that hill! PK/PD studies are a required part of drug development for every FDA-approved therapy. There are 1000s of people who do this type of work every day and it has a long history.

          Wrt mRNA vaccine (this is the same tech at the COVID vaccine, just with custom mRNA sequences), the mRNA is delivered by a carrier to the lymph nodes, which then sees the specific protein. Only then do the trained immune cells get a chance to go out and kill cancer cells.

          KLG also alluded to scaling this approach. If you take a look at the paper, it’s in collaboration with BioNTech (covid vaccine makers) and Genentech, so MSK is probably (one of) the clinical site and the commercialization will probably use their personalized mRNA vaccine manufacturing facilities. If these trials are successful, there’s no doubt they would be scaled out to meet demand.

      2. kareninca

        Weren’t we told that the spike protein from the covid vaccine would stay in one’s arm, at the shot site? I remember reading that stated with great confidence in many popular press articles that were meant to reassure. It was the weirdest thing. The idea was that it would never move to any other part of the body, like there was a big wall inside your arm. Then, if I remember correctly, the Japanese ran a study and found it in the ovaries.

        It’s funny, though, now I can’t seem to find those “stays in your arm” articles.

        1. Arizona Slim


          It was supposed to stay in the deltoid, all right. And that deltoid would be so-o-o-o immune to the ‘Rona that it wouldn’t be funny!

      3. tindrum

        Oz, that is just hand waving. Given that the mRNA was supposed to stay in the arm but has been found all over the body I do not know how you can state that “it is all known” without laughing.
        Also, the manufacturing process is so shoddy tthat the ampunt of RNA in each shot is unknowm, the fact that the vials were I think 4-shot vials or even 10 shot makes the game of chance even larger.
        If you feel that you can actually provide some evidence for your claim then go right ahead.

  3. Michaelmas

    Personalized RNA vaccines to stimulate an individual’s T cells against specific cancers was always the aim of, for instance, Moderna, in all the prospectuses for the company I saw since 2012-14. The Covid thing was a pragmatic improvisation.
    KLG: We need only vision and resolve to make them work in the wider clinical world.

    Well, one thing more: immense amounts of money.

    Something that most NC readers may not appreciate is how staggeringly expensive, forex, Phase 1, 2 and 3 trials can be. It happens regularly that a biotech startup with trials that produce satisfactory results can still get closed down around this point if they don’t have funders willing to continue underwriting them.

    And overall the cost of drug development is what maintains the current status quo of Big Pharma dominance of the medical-industrial. Individual biotech companies develop new therapies and technologies but frequently have to go to Big Pharma to get to market.

    …A pair of recently-released studies shed new light on the staggering cost of developing new drugs—an expense that now exceeds $2 billion per therapy on average.

    In one report, business services consultancy Deloitte details the growing research-and-development (R&D) expenses that biopharmas often blame for the sky-high list prices they charge for new treatments. Deloitte found that the average cost of developing a new drug among the top 20 global biopharmas it studied rose 15% ($298 million) last year, to approximately $2.3 billion ….

    1. Jeremy Grimm

      Perhaps drug discovery and development should not be handled by Big Pharma and the Market. Perhaps drug production and distribution should not be left to Big Pharma and the Market. If we had a government that worked for the people — a very big iff — perhaps the government might handle things as a component of providing Medicine as a component of providing for the Common Good.

      1. KLG

        Thank you, Jeremy. Beat me to it. There are some places private profit has no place. Health care, which should be a public good, is one of them. This includes the development of new drugs and treatments for diseases such as PDAC. We waste more than one thousand billion dollars a year on the Pentagon and its appurtenances. That money would go a long way for many nice things we cannot have…

        Just one little factoid I have mentioned here before. Eli Lilly collected about $300M, adjusted for inflation using the Bureau of Labor Statistics Inflation Calculator, for producing the Salk polio vaccine in the late 1950s. That vaccine stopped polio in its tracks, as did the Sabin vaccine a few years later. I am too lazy to look it up, but in the past two years Pfizer and the other COVID vaccine manufacturers have reported revenues in excess of $70B for vaccines that have worked at the margin, a little. For a while. “Nice” work if you can get it. And therein lies the problem.

      2. Michaelmas

        Jeremy Grimm: Perhaps drug discovery and development should not be handled by Big Pharma and the Market.

        Perhaps it should not. I personally am not a fan of Big Pharma. But the world is what it is and in particular in the US as currently constituted ….

        JG: If we had a government that worked for the people — a very big iff —

        You don’t have a government that works for the people. Period.

        Arguably, indeed, except for very short stretches of time, you never have. You’ve had a government that works for the oligarchs, ever since founding oligarchs G. Washington and T. Jefferson became supporters of US independence from the UK only once the Somerset case in 1772 and Dunmore’s proclamation in 1775 indicated the UK was going to abolish the slavery upon which their extensive wealth was predicated.

        Be the US and Big Pharma as they may be, this is a large problem. Let’s frame this problem another way and consider the alternative example of Israel’s Ashkelon nuclear desalination plant —
        The Future of Nuclear Desalination to Address Water Scarcity in Israel

        This nuclear desalination plant is not cost-effective by any commercial standards. Yet every Israeli fairly happily pays a chunk of taxes every year to support the effort because they understand that if the Jewish people — let us leave aside the emotive issue of the Palestinians for this discussion’s purposes — are to have a country where the desert blooms that in turn requires the water to make the deserts bloom, especially as the surrounding countries of the Middle East increasingly become water disasters.

        And so the Israelis make the communal effort.

        Conversely, in the US, the once-through fuel cycle was settled on because (1) recycling partially-used nuclear fuel would have cost the US energy companies more their potential profits and (2) recycling technology is also enrichment technology and the US military and nation-state wished to preserve as far as possible its nuclear weapons dominance over the rest of the world, so it did its best to prevent the proliferation of nuclear recycling.

        And so the US nuclear power effort has become the decades-long, failing bad joke that it has, with some 90,000 metric tonnes of radioactive waste piled up. The communal effort wasn’t there.

        Sadly, yet another instance of the inadequacy of the market-based, corporatocracy-centred approach to social organization and development is that currently, if a carbon-capture technology existed that in fact could pull carbon from the atmosphere on a global scale, there might nevertheless be no way to monetize that global-scale carbon capture.

        Seriously. I’m sure you’ll agree that’s a problem.

      3. tindrum

        It would be helpful if the FDA were not owned by big Pharma. Having private companies develop stuff for profit is one thing, allowing them to own the body that regulates them is just insane.

  4. Joe Well

    Thank you for sharing this good news. As the author states, good science done well.

    Sad that we are at the point that something like this has to be posted under a pseudonym. Has anyone studied how censorship and self-censorship are affecting medicine?

  5. Kouros

    My dream treatment for any cancer would be to be able to induce apoptosis in the cancerous cells. As in trying to convince out of control rambunctious teenagers full of zest for life at any cost to kill themselves…

  6. Smith, M.J.

    Thanks so much for this post, KLG.

    Unfortunately I have been riding the PDAC train for the last 15 months. A combination of chemo and radiation seems to have stalled its progress for now. You are right about the scary chemo cocktails—the side effects have been much worse than the disease so far.

    Luckily I live 30 minutes away from one of the foremost cancer treatment and research centers in the world. I have already taken part in 2 clinical trials, and my doctors are constantly on the lookout for others. Your article gives me hope to extend my train ride for a few more years at least.

    As Lambert would say, news you can use!

    1. KLG

      You’re welcome. I spent a significant period of 2022 taking a version of one of the drugs in that cocktail, along with radiation (which was much worse because of the target). I think it is safe to say this community will share in your hope for a long, comfortable, rewarding, and scenic train ride!

  7. Susan the other

    I always wondered, after stem cell therapy dropped out of the news with the caveat that stem cells are hard to control once injected and they can tour around, becoming anything they choose to be… if there isn’t some cellular mechanism inherent in both cancer and stem cells, just because they are both opportunists.

  8. Revenant

    Have I understood figure 3 (and the implied definition of RFS) correctly? In the neoantigen-responding group, no patient reached the median recurrence free survival implies no patient had yet died and therefore a survival time was not determined, I.e. everybody lived? Remarkable if true in pancreatic cancer.

    If that is not the right interpretation, what does median RFS not reached mean?

    1. KLG

      That is my understanding and I had the same initial reaction. The “survival curve” is flat because their was no “recurrence” during the time represented on the x-axis.

  9. Jeremy Grimm

    Vaccines use benign or at worst minimally harmful antigens to stimulate the immune systems. I believe there remains a great deal to discover about how mammalian immune systems work, how the immune systems of other animals work, and how plant immune systems work. I believe highlighting that lack of knowledge is one of the too many lessons to be learned from the mRNA vaccines applied to disease treatment, and most recently as a panacea for treating the Corona pandemic.

    I am concerned that viruses and other infectious agents are constantly evolving at rates that exceed the ability of higher life forms to evolve in response. Now, these times before the coming Collapse, are a most precious moment in the existence of Humankind — perhaps a defining — a pivotal moment. The resources exist in this moment to make momentous discoveries in basic Science, discoveries which may never again become possible to discover. The u.s. Empire has trained enormous cohorts of highly skilled, extremely intelligent, and devoted members of Humankind who desire little more than an opportunity to investigate and discover new Basic Science in numerous areas. The biological Sciences appear, to me, to be the most promising — although there are many areas of study, like the biological Sciences, that possess remarkable new tools, ample devotees, and they are ripe for major advances, if profits be damned — although profits from past efforts like putting Humankind’s footprints on the Moon have paid remarkable returns.

    Considering what will be possible after the Collapse, I have been trying, though with very limited success, to imagine what might still be possible. I fear NOW may be Humankind’s best and perhaps only hope to build the Science which might sustain the existence of Humankind into the far future.

  10. The Phoenix

    Why do we call it “vaccine”? The treatment looks promising and if it can be done at scale can be part of a multi-modal treatment regimen for cancer. But it’s not a vaccine.

    Leave vaccine as it is traditionally understood to prevent disease. Call it something else like “gene induced immune mediated therapy” with a fancy acronym. Not a vaccine.


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