University of Pittsburgh Cancer Institute (UPCI)

Cancer Immunoprevention

Tumor-associated Antigens The focus of this research theme is to identify and characterize prevention-relevant tumor antigens, and to develop animal models to test cancer immunoprevention strategies that are most likely to be translatable into applications for preventing cancer in high-risk individuals.

Selected Publications

  • Most tumor-associated antigens (TAA) are self-molecules that are abnormally expressed in cancer cells and become targets of antitumor immune responses. Antibodies and T cells specific for some TAAs have been found in healthy individuals and are associated with lowered lifetime risk for developing cancer. Lower risk for cancer has also been associated with a history of febrile viral diseases. A CIP study identified new antibodies against tumor cell proteins that were elicited by influenza infection. Furthermore, it was demonstrated that influenza experienced mice controlled tumor challenge better than influenza naïve mice, and that immunization with peptides derived from these proteins also prevented tumor growth. These data suggest that TAA are in fact disease-associated antigens that could be safely targeted by immunotherapy. (Iheagwara et. al., Cancer Immunol Res. 2014 Mar;2(3):263-73.)
  • Cancer vaccines based on human tumor-associated antigens (TAA) have been tested in patients with advanced or recurrent cancer, in combination with or following standard therapy. A collaborative clinical study between CIP and CEPP members showed that in patients without cancer but with a history of premalignant lesions (advanced colonic adenomas, precursors to colon cancer), a vaccine based on the TAA MUC1 was highly immunogenic in 17 of 39 (43.6%) of vaccinated individuals, eliciting high levels of anti-MUC1 immunoglobulin G (IgG) and long-lasting immune memory. Lack of response in 22 of 39 individuals was correlated with high levels of circulating myeloid-derived suppressor cells (MDSC) pre-vaccination. Vaccine-elicited MUC1-specific immune response and immune memory were not associated with significant toxicity. This study shows that vaccines based on human TAAs are immunogenic and safe and capable of eliciting long-term memory that is important for cancer prevention. We also show that in the premalignant setting, immunosuppressive environment (e.g., high levels of MDSC) might already exist in some individuals, suggesting an even earlier premalignant stage or pre-selection of non-immunosuppressed patients for prophylactic vaccination. (Kimura et. al., Cancer Prev Res. 2013 Jan;6(1):18-26.)

Members

Delgoffe, Greg, PhD
Immunology
Lakkis, Fadi, MD
Surgery
Ferris, Robert L., MD, PhD, FACS
Otolaryngology
Lu, Binfeng, MD, MS
Immunology
Finn, Olivera, PhD
Immunology
Thomson, Angus, PhD, DSc
Surgery