How COVID-19 Vaccines Could Open the Next Frontier in Cancer Treatment
The speed with which researchers developed safe, effective vaccines against COVID-19 was nothing short of miraculous. Historically, the research-and-development cycle for vaccines has been an arduous, uncertain, and time-consuming process. Yet in the span of just 11 months last year – from the WHO’s announcement on January 9 that mysterious cases of pneumonia had appeared in Wuhan, China, to the FDA’s Emergency Use Approval of the first COVID-19 vaccine on December 11 – scientists overcame a challenge that once took years or even decades. Indeed, the COVID-19 vaccines may spark a new era of vaccine innovation, one in which we can look forward not just to new ways to prevent infectious diseases, but also to preventative and therapeutic vaccines for conditions such as autoimmune disorders, genetic diseases and – perhaps most promising – cancer.
Most people are familiar with preventative vaccines, which protect against disease. When it comes to cancer, there is already one in wide use. The HPV vaccine stimulates an immunological barrier to human papillomavirus, a virus that can cause cervical and other forms of cancer. As early as the mid-1800s, however, there have been clues that the immune system can be harnessed to fight cancer directly (1). And today, research is accelerating into therapeutic vaccines that can help the body fight off a cancer that has already developed, and/or prevent it from returning or progressing after other treatments, such as chemotherapy, radiation or surgery.
Though not entirely intuitive, cancer is, in many ways, an immunological disease. Approximately 5%, or two trillion, of our ~37.2 trillion cells (2) divide every day, and every time they do, they have to replicate their three billion base pairs of DNA. While our cells are incredibly accurate copiers, mistakes do happen, and when they do, cancer can develop. And while our immune system is wired to recognize and destroy cancer cells, unfortunately many cancer cells are wired to escape immune detection. This dichotomy is the crux of the challenge of developing effective cancer vaccines. Recent studies, however, suggest that therapeutic cancer vaccines can be successful in the right circumstances, such as when disease burden is low, a robust and sustainable immune response to the vaccine is achieved, and immunosuppression is minimal. The trick is to use the right vaccine in the right person at the right time.
This is easier said than done, but emerging research is arming us with the information we need to be more successful than ever before.
Types of therapeutic cancer vaccines
All vaccines contain a substance that resembles a disease-causing agent. For cancer, that means vaccines might contain material taken directly from the cancer cells themselves (e.g., cell lysates), or synthetic components of the cells, such as DNA, RNA or peptides. Either way, these vaccines teach the immune system how to recognize features of cancer cells that are distinct from normal cells, just like vaccines for infectious diseases teach the immune system how to recognize an infectious agent, such as a virus or bacteria. Historically, most cancer vaccines have either been made from the patient’s own tumor cells or based on “shared antigens,” meaning they were composed of peptides common in certain cancers. Today, more personalized approaches, called neoantigen vaccines, are also in development, where the vaccine is composed of DNA, RNA or peptides that contain a selection of the exact genetic alterations present in an individual’s cancer cells.
Therapeutic cancer vaccines have been in development for decades. In 2010, the first (and only) therapeutic cancer vaccine, Sipuleucel-T, or Provenge, was approved by the FDA. Provenge extends survival in metastatic prostate cancer patients by approximately four months (1). Though its application might be narrow and its impact limited, this achievement at the very least demonstrated that therapeutic cancer vaccines can improve outcomes in cancer patients, inspiring further research. In the past decade, tremendous progress has been made toward understanding how to optimize vaccine design and minimize immune suppression and escape (2). For example, in a study out of the Dana Farber Cancer Institute, a neoantigen vaccine prevented cancer recurrence in high-risk melanoma patients, and immune responses to the vaccine remained active for four years (and counting) (3). In another study out of Spain, a tumor lysate vaccine extended disease-free survival in colon cancer patients by over a year (4). And in patients with one of the deadliest cancers, glioblastoma, one vaccine extended overall survival by almost five months.
COVID-19 has been devastating, but if there are any silver linings, the unprecedented development of effective vaccines in less than a year is surely among them. By demonstrating what can be accomplished through concerted effort and adequate resources, those strides should further propel research and development in therapeutic cancer vaccines, which offer hope and improved outcomes for millions of cancer patients around the world.
* Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.
(1). Kantoff, P. W. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363, 411-422, doi:10.1056/NEJMoa1001294 (2010).
(2). Saxena, M., van der Burg, S. H., Melief, C. J. M. & Bhardwaj, N. Therapeutic cancer vaccines. Nature Reviews Cancer 21, 360-378, doi:10.1038/s41568-021-00346-0 (2021).
(3). Hu, Z. et al. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nature Medicine 27, 515-525, doi:10.1038/s41591-020-01206-4 (2021).
(4). Rodriguez, J. et al. A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis. J Immunother Cancer 6, 96, doi:10.1186/s40425-018-0405-z (2018).