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Indian-origin scientist develops groundbreaking mRNA vaccine against pancreatic cancer

Dr. Kamal Kant KohliWritten by Dr. Kamal Kant Kohli Published On 2025-03-12T08:15:33+05:30  |  Updated On 12 March 2025 2:39 PM IST
Indian-origin scientist develops groundbreaking mRNA vaccine against pancreatic cancer
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An Indian origin scientist Vinod Balachandran, MD, in latest data from the phase 1 trial has revealed that an investigational therapeutic mRNA vaccine can mobilize anti-tumor T cells that may recognize pancreatic cancers as foreign, potentially years after vaccination.

A new study in Nature highlights promising results for autogene cevumeran, a personalized mRNA-based cancer vaccine for treating pancreatic cancer. This therapeutic vaccine stimulates the immune system to fight existing cancer and may reduce the risk of recurrence after surgery.

The study, led by Dr. Vinod Balachandran who is a pancreatic cancer surgeon-scientist at Memorial Sloan Kettering Cancer Centre, brings new hope to patients fighting one of the most lethal cancers.

Pancreatic cancer has one of the lowest survival rates, with only about 13% of patients living five years post-diagnosis. Existing treatments like chemotherapy, radiation, and targeted therapies have limited effectiveness against this aggressive disease, highlighting the urgent need for new options. Autogene cevumeran, a personalized vaccine, is tailored to each patient based on their tumor’s unique mutations. This approach helps train the immune system to identify and attack cancer cells, similar to how vaccines combat viruses.

A key challenge for cancer vaccines is producing long-lasting functional T cells that target tumor antigens. This study reveals that mRNA-lipoplex vaccines targeting neoantigens from somatic mutations could overcome this hurdle in pancreatic ductal adenocarcinoma (PDAC), a highly lethal cancer with limited mutations.

New results from the phase 1 clinical trial show that the therapeutic cancer vaccine activated tumor-specific immune cells that persisted in the body up to nearly four years after treatment in some patients. In addition, patients with a vaccine-induced immune response had a reduced risk of the cancer coming back at a three-year follow-up compared with patients whose immune systems did not respond.

“The latest data from the phase 1 trial are encouraging,” says Vinod Balachandran, MD, principal investigator of the trial and senior author of the new publication. “They suggest this investigational therapeutic mRNA vaccine can mobilize anti-tumor T cells that may recognize pancreatic cancers as foreign, potentially years after vaccination.”

Dr. Balachandran is a pancreatic cancer surgeon-scientist in the Human Oncology and Pathogenesis Program and Director of The Olayan Center for Cancer Vaccines (OCCV) at Memorial Sloan Kettering Cancer Center (MSK). The OCCV is a research hub that spans the full spectrum of basic discovery to clinical application of cancer vaccines.

The phase 1 study tested autogene cevumeran (BNT122, RO7198457), a therapeutic mRNA cancer vaccine developed and researched through a collaboration between BioNTech, an immunotherapy company, and Genentech, a member of the Roche Group.

The therapeutic mRNA cancer vaccine was personalized for each of the 16 participants in the trial based on the mutational profile of each patient’s tumor. As reported in2023 in Nature, the vaccine was safe with no serious side effects and stimulated an immune response in half of patients.

Therapeutic cancer vaccines such as autogene cevumeran are designed to treat-not prevent-cancer. By delivering proteins found exclusively in cancer (called neoantigens), these vaccines aim to train the immune system to recognize cancer cells as foreign.

Therapeutic cancer vaccines that can stimulate a robust, long-lived immune response with clinical impact have remained largely elusive. But recent research and technological developments in mRNA technology are changing the field. This approach is primarily aimed at the early stages of cancer, where the cancer has not yet spread and tumors can be surgically removed, to help delay or prevent recurrence.

In these findings from the phase 1 trial, the researchers could detect vaccine-stimulated T cells at substantial frequencies up to nearly four years after treatment. The team was able to track the vaccine-induced T cells with the help of computational biologist Benjamin Greenbaum, PhD.

The vaccine-stimulated T cells retained their anti-cancer activity, even after patients received chemotherapy following initial doses of the vaccine. Researchers had wondered whether chemotherapy might somehow diminish the effects of the vaccine. It did not seem to in this small, early study.

“For patients with pancreatic cancer, our latest results continue to support the approach of using personalized mRNA vaccines to target neoantigens in each patient’s tumor,” Dr. Balachandran says. “If you can do this in pancreas cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”

Pancreatic cancer is one of the deadliest cancers, even for patients whose tumors are removed with surgery. Only about 13% of patients are alive five years after diagnosis, according to the American Cancer Society. Chemotherapy, radiation, targeted therapy, and current immunotherapies are also largely ineffective against pancreatic cancer, so new therapies are urgently needed for patients who face this disease.

Dr. Balachandran’s team in the OCCV aims to innovate next-generation cancer vaccines, with initial goals to expand vaccine use in pancreatic and other cancers lacking effective treatments.

New Clinical Trial Results for mRNA Pancreatic Cancer Vaccine

The investigator-initiated, single-center phase 1 clinical trial involved studying 16 MSK patients who received the investigational therapeutic cancer vaccine autogene cevumeran, along with an immunotherapy drug calledatezolizumab and a chemotherapy regimen called mFOLFIRINOX. Early immunological and clinical results from the trialpublished in Nature in 2023 showed this treatment was generally well tolerated and stimulated an immune response that correlated with delayed recurrence at a 1.5-year median follow-up compared with non-responders.

Results at a three-year median follow-up, now published, show:

  • The investigational cancer vaccine activated a T cell response in half of patients (responders), and this response correlated with delayed recurrence at three-year post-treatment follow-up compared with non-responders. Researchers do not yet know if the vaccine caused the delay in cancer recurrence; investigating this question is a goal of an ongoing randomized phase 2 clinical trial.
  • Of the eight patients whose immune systems responded to the vaccine during the study period, six have not seen their cancers return during the follow-up period. The other two patients relapsed. These patients with relapse showed weaker vaccine-induced T cell activity compared with other responders.
  • By studying tissue and blood from these patients before and after the vaccine was given, the team found that the majority of T cells had been newly stimulated by the vaccine, as these T cells were undetectable before vaccination. In addition, the majority of these vaccine-induced T cells persisted beyond two years post-vaccination and maintained anti-cancer function in some patients.

Reference:

Sethna, Z., Guasp, P., Reiche, C. et al. RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. Nature (2025). https://doi.org/10.1038/s41586-024-08508-4.

Naturepancreatic cancercancermRNA Vaccine
Source : Nature
Dr. Kamal Kant Kohli
Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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