Nicht-mRNA-Impfstoff-Targeting gemeinsame Mutationen bei Bauchspeicheldrüsen- und Darmkrebserkrankungen könnten ein Gewinnungsrisiko eines Rückfalls senken | Lymphknoten-zielgerichtete, mKRAS-spezifische Amphiphil-Impfstoff bei Pankreas- und Darmkrebs: Phase 1 Amplify-201-Studie Endergebnisse

Key section from the news report:

>Many cancer vaccines, including some of those based on mRNA technology, are personalised to the patient’s tumours.
>
>However, a study has suggested a non-personalised, experimental vaccine that is already being made at scale could help prevent the return of pancreatic and colorectal cancer.
>
>If borne out by further trials, experts say, the approach could be beneficial since the vaccine is likely to be cheaper and faster to access than mRNA jabs, as well as less toxic than some other therapies.
>
>“After a long-term follow-up of this study, we were able to demonstrate that the group of patients who mounted an immune response have a greater likelihood of not having their cancer return and living longer compared to historical expectation of what that patient would do,” said Prof Zev Wainberg, an oncologist at the University of California, Los Angeles, and a co-author of the study.
>
>The authors noted 90% of people with pancreatic cancer and 50% of those with colorectal cancer had mutations in the Kras gene. These mutations result in the production of altered Kras proteins that cause cells to divide and proliferate.
>
>Writing in the journal Nature Medicine, Wainberg and colleagues reported how they gave a vaccine called ELI-002 2P to 20 patients who had had surgery for pancreatic cancer and five who had been operated on for colorectal cancer.
>
>The vaccine contains peptides – long chains of amino acids, which are the building blocks of proteins. The vaccine works by training the T-cells of the body’s immune system to recognise and kill cancer cells with mutations that result in them producing the altered Kras proteins.
>
>At a median follow-up of almost 20 months, the team found patients fell into two groups: 17 who had a strong immune response to the jab and eight who had a weaker response.
>
>The team found the former group experienced a longer period before their cancer returned and survived longer overall. Overall, four of those 17 patients died during follow-up, compared with seven of the eight who had a lower immune response.
>
>However, the study is early stage research designed primarily to assess safety, involved only 25 participants, had no controls, and looked at two very different types of cancer.

—

Research link: [Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results](https://www.nature.com/articles/s41591-025-03876-4)

Abstract:

>Cellular immunity, mediated by tumor antigen-specific CD4+ and CD8+ T cells, has a critical role in the success of cancer immunotherapy by targeting intracellular driver and passenger tumor mutations. We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (n = 25, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. At a median follow-up of 19.7 months, efficacy correlated with mKRAS-specific T cell responses above or below a threshold 9.17-fold increase over baseline, with median radiographic relapse-free survival not reached, versus 3.02 months (hazard ratio (HR) = 0.12, P = 0.0002) and median overall survival not reached versus 15.98 months (HR = 0.23, P = 0.0099). Seventy-one percent of evaluable patients induced both CD4+ and CD8+ subsets, with sustained immunogenicity. Following ELI-002 2P treatment, antigen spreading was observed in 67% of patients, with increased T cells reactive to personalized, tumor antigens absent from the ELI-002 2P vaccine. Therefore, lymph node-targeting amphiphile vaccination induces persistent T cell responses targeting oncogenic driver KRAS mutations, alongside personalized, tumor antigen-specific T cells, which may correlate to clinical outcomes in pancreatic and colorectal cancer.