Autogene Cevumeran (BNT122) mRNA Cancer Vaccine Shows 86% Reduction in Pancreatic Cancer Recurrence Risk in Phase 1 Trial Published in Nature

Recently, a research team led by scientists from Memorial Sloan Kettering Cancer Center (MSKCC) published the latest results of the Phase 1 clinical trial for the personalized neoantigen vaccine autogene cevumeran (BNT122), jointly developed by BioNTech and Roche (Roche), in the journal *Nature*. The trial results showed,In patients with pancreatic ductal adenocarcinoma (PDAC) who have undergone surgical resection of tumors, this mRNA-based neoantigen vaccine continuously reduces the risk of disease recurrence.At a median follow-up time of 3.2 years, PDAC patients who responded to autogene cevumeranThe risk of disease recurrence was reduced by 86% compared to patients who did not respond!

▍Vaccine responders have an 86% reduced risk of recurrence

Autogene cevumeran is a personalized cancer vaccine tailored for each cancer patient.It is an individualized neoantigen vaccine generated based on the powerful technical platform of US-based BioNTech. It can encode dozens of neoantigens, stimulate a comprehensive immune response in the human body against tumor cells, and prevent tumor cells from evading attacks by the immune system.

On May 10, 2023, the 1.5-year median follow-up data was initially published and appeared in the prestigious international journal *Nature*, causing a significant stir. The updated 3-year follow-up data presented at the 2024 AACR conference continued to show that administering the personalized mRNA cancer vaccine Autogene cevumeran (codenamed BNT122, RO7198457) as an adjuvant treatment after surgery can delay the recurrence of pancreatic cancer in patients.The study also shows that the median lifespan can be extended to 6 years after a single vaccine booster shot!

From December 2019 to August 2021, a total of 34 pancreatic cancer patients were recruited, of which 28 underwent surgery. Nineteen received atezolizumab treatment, and 16 of these patients were administered the autologous mRNA neoantigen vaccine cevumeran. Fifteen of these 16 patients also received subsequent mFOLFIRINOX chemotherapy.

Results:

• Eight out of 16 patients (50%) who received the vaccine generated a T-cell response and were considered responders to the mRNA neoantigen vaccine cevumeran. This means the vaccine taught their immune system how to recognize and eliminate cancer cells, preventing tumor recurrence.

• In patients with an immune response, more than 80% of the vaccine-induced neoantigen-specific T cells remained detectable within 3 years after administration. Compared to non-responders (13.4 months), the median recurrence-free survival in these patients was significantly prolonged (not yet reached).

• Six of eight patients who had an immune response to autologous cevumeran remained disease-free during the three-year follow-up, while seven of eight patients who did not have an immune response to the treatment during the trial experienced tumor recurrence.

• In blood tests, all eight responders produced T cells targeting their tumors. These activated, highly potent killer T cells persisted in the body for at least two years despite subsequent chemotherapy.

On February 19, 2025, the latest results of this Phase 1 clinical trial were once again published in Nature, showing that: the therapeutic cancer vaccine activated tumor-specific immune cells, which could persist for up to nearly four years in some patients. Moreover, compared with patients who showed no immune response, those with a vaccine-induced immune response had a lower risk of cancer recurrence during three years of follow-up. This experimental therapeutic mRNA vaccine mobilizes anti-tumor T cells, which may recognize pancreatic cancer as foreign cells years after vaccination.

Moreover, among responders, the average estimated lifespan of CD8+ T cell clones induced by the gene cevumeran was 7.7 years (ranging from 1.5 to approximately 100 years), with about 20% of the clones having a latent lifespan of several decades, potentially longer than the host's survival time. In each patient, 86% of the clones persisted at relatively high frequencies for approximately three years after vaccination, including clones with high affinity for PDAC neoantigens. Therefore, this vaccine may delay the recurrence of pancreatic cancer!

▍Neoantigen Cancer Vaccine

Autogene cevumeran is an individualized neoantigen vaccine generated based on BioNTech's iNeST cancer vaccine technology platform.Neoantigens are mutant proteins generated based on tumor-specific mutations. These mutant proteins are recognized as foreign substances by the human immune system, which then triggers an immune response against them.

The Development Strategy of Personalized Cancer Vaccines isIdentifying new antigens specifically expressed in cancer cells due to genetic mutations in cancer patients through methods such as gene sequencing., further utilizing these new antigens to activate T cells and promote their proliferation. The activated T cells can migrate to the vicinity of the tumor and attack it.

Recent years have seen multiple advancements in the field of neoantigen cancer vaccines. Earlier this month, a research team led by scientists from Yale University and the Dana-Farber Cancer Institute published the latest findings on personalized cancer vaccines (PCV) in the journal *Nature*.Nine high-risk renal cell carcinoma (RCC) patients received treatment with PCV targeting neoantigens (with or without adjuvant immunotherapy ipilimumab) after undergoing resection surgery. Clinical trial results showed that at a median follow-up time of 40.2 months, all nine patients had no recurrence of cancer.

In addition,The mRNA individualized cancer vaccine mRNA-4157, jointly developed by Moderna and Merck, is currently being evaluated in multiple late-stage clinical trials for the treatment of various cancer types, including high-risk melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and cutaneous squamous cell carcinoma.It has recently been rated by the industry media Evaluate as one of the potential blockbuster R&D pipelines worth watching. We look forward to the smooth clinical development of therapies under research in the cancer vaccine field, which will soon become an innovative treatment option for cancer patients.

Source: WuXi AppTec, Global Oncology Consultancy