The Promise of Cancer Vaccines: A Vision of What Biotech Can Be
Jennifer Phillips provides a comprehensive breakdown of a potential cancer vaccine, and the role biotech has in its development.
Written by: Jennifer Phillips
The Resurgence of Cancer Vaccines
We appear to be rounding another corner in the immunotherapeutic treatment of a range of cancers. Two of the common barriers faced by cancer immunotherapies are the immunosuppressive effects of indolamine 2,3 dioxygenase (IDO) and programmed death-ligand 1 (PD-L1), two proteins produced by many cancer cells, and which prevent endogenous immune responses from targeting them. To offer an over-general summary, IDO and PD-L1 make cancers invisible to T cells. That has made them a natural target for anti-cancer drugs called “immune checkpoint inhibitors,” which might – for instance – block PD-L1’s receptor protein on T cells to prevent it from disrupting their function, allowing them to target cancers normally.
But those immune checkpoint inhibitors have produced mixed results. IDO inhibitors in particular generated tremendous excitement for several years before a string of high-profile clinical failures – including Incyte’s epacadostat and a similar drug from NewLink Genetics – dampened enthusiasm and slowed research.
IO Biotech received an FDA breakthrough therapy designation and completed a hugely successful round of Series B funding for a new alternative. Rather than targeting IDO directly, their treatment helps T cells overcome immunosuppressive effects. The treatment is part of a growing interest in neoantigen-based vaccines that activate T cells and direct them toward cells that express certain proteins, such as IDO and PD-L1, effectively pointing them straight toward cancer cells. As a group, this category of vaccines is already several years old, but the IO Biotech approval represents a significant leap forward.
Before getting into the details of why the new treatment is so significant, it’s worth explaining just how promising and just how powerful these vaccines appear to be.
First, immunotherapies, in general, are more targeted, more sustainable, far safer, and have fewer side effects than other anti-cancer treatments like radiotherapy and chemotherapy. Second, the immune cells they rely on are endogenous and already present; the therapies function only to help them identify and remember cancer cells. Immunotherapies are often combined. For instance, immune checkpoint inhibitors are often combined with T cell therapies. Just a few years ago, those were the leading immunotherapies for cancer.
Among that group, cancer vaccines have slowly been gaining more attention. Their major benefit is that they allow T cells’ highly selective activation and direction, but their development has faced significant barriers. Cancer patients often have severely weakened immune systems. Cancer cells tend to develop multiple highly effective immunosuppressive functions, and to reach clinical efficacy, the vaccines need to stimulate sustained, extremely high-volume immune response.
The most promising recent vaccines have helped solve those problems by switching from targeting tumor-associated antigens (self-antigens expressed at higher rates by cancer cells) to tumor-specific antigens, including neoantigens. The results from early clinical trials have been promising: “robust tumor-specific immunogenicity and preliminary evidence of antitumor activity.”
A Leading Candidate
A few years ago, a review in Clinical Cancer Research argued that the most promising of these emerging vaccine candidates used dual-action platforms that targeted both cancer cells and the immunosuppressive tumor microenvironment. Those platforms included viruses capable of heterologous prime-boost antigen delivery, certain nanoparticle systems, and IO Biotech’s proprietary T-win platform.
It’s no coincidence that one of the study’s authors is the founder and CEO of IO Biotech, Mai-Britt Zocca. In the two years since her company has invested heavily in the technologies for rapid sequencing and neoantigen selection that allow for personalized vaccines. That investment appears to have paid off, as evidenced by the results of the Phase I/II clinical trial MM1636, presented at the European Society for Medical Oncology Virtual Congress 2020.
The trial used a novel vaccine combining long peptide sequences derived from IDO and PD-L1. In combination with the PD-1 blocker nivolumab, 15 doses of the vaccine over the course of a year yielded promising results: a 79% overall response rate (94% for patients whose tumors expressed PD-L1) with 45% of participants exhibiting a complete response (i.e., the total elimination of their tumors). For comparison, nivolumab alone produced only a 45% overall response and 19% complete response in a separate trial.
The FDA approval and the Series B funding both came through on the strength of those numbers. The funds are being used for a large, ongoing Phase II trial. This is cause for celebration and a reminder of the reason we do what we do. At its best, biotech is extraordinary.
Jennifer Phillips originally wrote this article. Have questions? Get in touch!
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