David Munn is a Professor of Pediatric Hematology-Oncology at the Medical College of Georgia. He received his undergraduate degree in Philosophy from Mercer University and his MD degree from the Medical College of Georgia in 1984. Following Pediatric residency at Rainbow Babies’ and Children’s Hospital and a Fellowship in Pediatric Hematolo-Oncology at Memorial Sloan-Kettering Cancer Center, Dr. Munn returned to the Medical College of Georgia in 1990. He was a founding member of the Immunotherapy Center at MCG, is a member of the Cancer Immunotherapy Program at the Georgia Cancer Center, and is a Senior Advisor to the Director. Dr. Munn’s laboratory focuses on basic research in tumor-induced immune tolerance, the IDO pathway, and Treg activation. His translational focus is on activating antigen cross-presentation and endogenous T cell responses in the tumor, with an emphasis on combining standard-of-care chemotherapy and radiation with novel orally-bioavailable small-molecule immune modulators.
What are the two or three critical issues facing cancer immunotherapy?
From my perspective, the field is faced with two key issues – one scientific, and one practical – that currently limit our ability to take full advantage of the power of immunotherapy. The first issue is the need to reconfigure the tumor microenvironment to allow robust, highly immunogenic cross-presentation of endogenous tumor antigens, so as to activate an aggressive polyclonal T cell response against the patients’ own tumor antigens. This endogenous cross-presentation needs to occur whenever tumor cells die – whether due to immunotherapy, immunogenic chemotherapy, radiation, or T cell adoptive-transfer. Unless the unique and “personalized” antigens released from the patient’s dying tumor cells are treated by the immune system as robustly immunogenic, rather than anergizing and tolerizing, then patients will not be able to develop the long-term self-sustaining, self-amplifying polyclonal response that is needed to avoid resistance and create cures. The second, more immediate practical need, is to develop synergistic, mechanistically-based strategies for integrating immunotherapy with standard-of-care chemotherapy and radiation. Ideally, the goal is not to force an “either/or” choice between well-accepted standard treatments versus new immunotherapy, but rather to exploit chemotherapy and radiation as built-in immune adjuvants to enhance the response to our immunotherapy.
How do you feel the Society for Immunotherapy of Cancer would benefit from your involvement as an At-Large Director on the Board?
As a pediatric oncologist, I am acutely aware of the need to seamlessly integrate immunotherapy approaches with standard-of-care conventional regimens. Pediatric patients are good examples in this regard, because children have wonderful immune systems, and they also have highly effective standard-of-care regimens – often even in the relapsed setting. Thus, if we are going to take advantage of the power of immunotherapy, we need to find ways to integrate it fully with chemotherapy and radiation – ideally from the very beginning of therapy. This concept is just as true for adults as it is for pediatrics. Fortunately, increasing preclinical research supports the hypothesis that not only is immunotherapy compatible with chemotherapy and radiation, but each modality can be highly synergistic for the other. In this regard, I bring a slightly different perspective to the discussion, because my research has a long-standing focus on “up-stream” mechanisms such as IDO, tolerogenic APCs, and Treg/APC interaction, which control the initial, fundamental decision between either activating T cells or tolerizing them. This up-stream focus nicely complements the more “T cell-centric” perspective that focuses on T cell checkpoints and adoptive-transfer approaches. I believe that empowering the patient’s endogenous antigen-presenting milieu in the tumor microenvironment is going to be a critical challenge in the coming years, as we try to activate the patient’s own T cell repertoire to mediate life-long disease control and eradication.