A Personalized mRNA Vaccine Breakthrough for Pancreatic Cancer

Cancer Vaccines: A Remarkable Step Forward

The central goal of the precision medicine field is to treat disease more effectively by taking a personalized approach that capitalizes on the unique features of a given patient or group of patients. Cancer, which is one of the most heterogenous diseases, is a prime target for testing and validating this approach.
All cancer cells are mutated, and those mutations will produce unique alterations to proteins expressed by the cancer cell. Using genomic sequencing of an individual patient’s tumor, researchers can identify the exact mutations present and design a vaccine to target the altered parts of the affected proteins, called neoantigens. The result, a custom neoantigen vaccine, can prime the immune system to attack the neoantigens of the cancer cells that it had not previously flagged as a threat.

New Neoantigen Vaccine Stimulates T Cells in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is lethal in 88% of patients. It remains one of the most challenging cancers to treat or detect early, but researchers found that it contains neoantigens that are amenable to this new class of vaccines. In a recent paper published in Nature, a research team from the Memorial Sloan Kettering Cancer Center led by Dr. Vinod Balachandran completed a phase I trial of a neoantigen vaccine combination therapy in patients with surgically resected PDAC tumors.

Following surgery, 16 patients were treated first with an anti-PD-L1 immunotherapy followed by a custom neoantigen vaccine containing up to 20 neoantigens. Fifteen of the patients were then also treated with a 4-drug combination chemotherapy. Of the original 16 patients, 8 patients had induction of high-magnitude, neoantigen-specific T cells. Immune responders had longer recurrence-free survival at an 18-month benchmark than non-immune responders who had a median of 13.4 months of recurrence-free survival.

Future Work

In such a deadly cancer like PDAC, this is a major result, providing new hope for treatment improvement. PDAC is known to be an “immune cold” tumor, making it very challenging to treat with immunotherapy alone. The authors investigated the T cell response induced by vaccine treatment, identifying T cell clonal expansion using T cell receptor sequencing of peripheral blood. Single cell RNA sequencing (scRNA-seq) confirmed that the vaccine-induced expansion of CD8+ T cells induced cells that were able to successfully infiltrate tumors and make them more immunogenic, meaning more “visible” for the immune system to target.
The promise of neoantigen cancer vaccines is rapidly expanding, as evidenced by Merck and Moderna’s recent phase II trial of a vaccine for melanoma, also with promising results. With continued investment in mRNA vaccine technology, optimism is high that results like increased progression-free survival lengths will continue to improve.

Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help

Groundbreaking studies like these are made possible by technological advances making biological data generation, storage and analysis faster and more accessible than ever before. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey.
As experts across data types from leading sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here to schedule a free introductory call with a member of our team.

Jane Cook, Biochemist & Content Writer, Bridge Informatics

Jane Cook, leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas. While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email jennifer.martinez@old.bridgeinformatics.com or dan.ryder@old.bridgeinformatics.com.

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