Interview with CCSA’s immunologist-in-residence Dr. Lata Mukundan.

Q: What are some of the most promising agents you are currently working with?
A: Cancer preventive agents, particularly vaccines are some of the most promising agents I work with.

Q: How do cancer preventive vaccines work/how are they designed to work?
A: Cancer preventive vaccines work to stimulate the immune system and initiate a process culminating in the destruction of a cancer cell. Vaccines have the potential to provide long-lasting immunity in the absence of toxicity, with minimal dosing, and at low cost. Ideally, an effective cancer vaccine would induce a persistent, long-term response, characterized by immunological memory, to counteract the incessant generation of neoplastic (i.e., new and abnormal) cells that develop throughout an individual’s lifetime.

Q: What are adjuvants and how are they used in cancer preventive vaccines?
A: In order for vaccines to stimulate appropriate immune responses, they have to be presented by antigen presenting cells in the context of appropriate co-stimulatory signals. If not, the vaccine would have the opposite effect of tolerizing rather than stimulating the immune system. The adjuvant selected depends on the kind of immune response that is desired and the delivery system chosen for the vaccine.

Q: What types of patients receive cancer preventive vaccines?
 A: Vaccines such as Gardasil 9, to prevent HPV-associated anogenital cancers, and Recombivax-HB, to prevent HBV associated liver cancers, are safe to be administered in healthy individuals and are approved for use in the United States. All other cancer-preventive vaccines are now in clinical development only.

Q: What types of vaccines are being studied in clinical trials?
A: Therapeutic vaccines have been tested since the dawn of the century mostly in advanced cancer patients and have by and large been unsuccessful due to a suppressed and derailed immune system, a characteristic feature of advanced cancers. An attempt is now being made to investigate cancer vaccines in a preventive setting, mostly in the adjuvant setting (i.e., prevention of recurrence). There may be opportunities in the future to test vaccines in a primary prevention setting.

Q: In your opinion, where do you think research is headed for a specific vaccine or cancer preventive vaccine research in general?
A: Recreating the success of infectious disease vaccines to prevent all cancers would be the ultimate goal although a pipe dream at this point. The advent of modern technologies (imaging, cell free DNA, circulating DNA, etc.) and ground breaking initiatives such as the Cancer Moonshot 2020 and Pre-Cancer Genome Atlas will undoubtedly drive the field of cancer immunoprevention forward. In the future, it may be possible to use a non-invasive test identify people in very early stages of cancer and give them a “personalized” vaccine based on the molecular profile of their lesion to halt disease. Individuals at high risk of developing cancer, either because of their genetic make-up (BRCA1 mutations) or lifestyle (obesity, smoking), may represent ideal candidates to receive a cancer preventive vaccine.

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