Progressnotes - January/February 2013 - (Page 10)
Immunotherapeutic Approaches to Cancer, Part I:
Training the Immune System to Better Detect and Target Tumor Cells
FIGURE 1. Activation of a T cell by a dendritic cell.
ince vaccines became available for infectious diseases, we’ve had this dream of a vaccine for cancer,” notes Zihai Li, M.D., PhD, who holds the Abney Chair Remembering Sally Abney Rose in Stem Cell Biology & Therapy and serves as Chair of Microbiology & Immunology at MUSC. With recent advances in genomics and the knowledge base gained during the past twenty years about how tumors and the various components of the immune system work, Dr. Li believes that “Immunotherapy for cancer is not just a fantasy or wild dream anymore.” Basic research findings are beginning to filter into clinical trials. David Cole, M.D., Chair of Surgery and Director of the Center for Cellular Therapy at MUSC, and the tumor immunology team at Hollings Cancer Center, including Zihai Li, M.D., PhD (program leader), Shikhar Mehrotra, PhD, Mark Rubinstein, PhD, and Chrystal Paulos, PhD, have been working to develop immunotherapeutic techniques in the laboratory that have clinical relevance, and their work is beginning to bear fruit. Dr. Cole is currently the Investigational New Drug Principal Investigator on three phase 1 clinical trials of dendritic cell vaccines open at Hollings Cancer Center, two in patients with metastatic or locally advanced pancreatic cancer (Principal Clinical Investigator: Steven H. Chin, M.D.) and one in patients with metastatic melanoma (Principal Clinical Investigator: Keisuke Shirai, M.D.).
The Basics of Tumor Immunology
The body’s immune system protects us both against invading pathogens, such as viruses, and against mutated cells within our own bodies (eg, cancer) via immune surveillance. Lymphocytes, particularly T lymphocytes or T cells, are on guard against new antigens and, upon detection, mount a defense against them. When activated, CD8+ T cells are the “killer” cells of the body, charged with purging it of any enemy invaders or internal threats. Unlike viruses, which can easily be identified as “foreign,” cancer derives from self and so can be much harder for T lymphocytes to detect. It is adept at cloaking itself, hiding in plain sight and tricking the T cells into thinking that it does not require their attention. In other words, the tumor creates an immunosuppressed environment around it, and the T cells in that area become “tolerant” of it, unable to recognize it as an enemy and/or to mount an effective response. According to Dr. Cole, “It’s sort of a like an army of soldiers standing around. Until someone sets the alarm, they are not going to go into action to activate, divide, proliferate and attack.” Retraining the body’s immune system to set that alarm so that T cells can mount an effective attack against tumors is one of the principal aims of immunotherapeutic approaches to cancer. Something must be done to “break the tolerance,” ie, to overcome the
Progressnotes January–February 2013
MUSC’s Medical Magazine
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