|Education||MS, Massachusetts Institute of Technology|
Cancer immunotherapies, which harness the immune system to fight cancer, hold great promise for improving the prognosis of a number of cancer types. While some immunotherapies broadly activate the immune system to fight cancer, these can potentially lead to autoimmune side effects. I am interested in developing tumor-specific immunotherapies by targeting mutations present only in the tumor cell. Most mutated proteins are intracellular, and thus difficult to target. However, a subset of mutation-containing peptides resulting from degraded proteins are present in the context of HLA molecules on the cell surface. Tumor-reactive T lymphocytes recognize these cancer-specific “neopitopes,” however not all patients have a broad enough repertoire of tumor-reactive T cells to mount an effective anti-tumor response. Thus, I am using phage display technology to generate TCR-mimic antibodies specific to mutant peptide-HLA complexes. Like the T-cell receptor (TCR) found on T-cells, TCR-mimic antibodies recognize a particular peptide-HLA complex, and can be used in a variety of therapeutic and diagnostic modalities.
- Perica K, Bieler JG, Schütz C, Varela JC, Douglass J, Skora A, Chiu YL, Oelke M, Kinzler K, Zhou S, Vogelstein B, Schneck JP. “Enrichment and Expansion with Nanoscale Artificial Antigen Presenting Cells for Adoptive Immunotherapy.”ACS Nano. 2015 Jul 14. PMID 26171764
- Skora AD*, Douglass J*, Hwang MS*, Tam AJ, Blosser RL, Gabelli SB, Cao J, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Zhou S. “Generation of MANAbodies specific to HLA-restricted epitopes encoded by somatically mutated genes.” Proc Natl Acad Sci U S A.2015 Jul 27. PMID 26216968 [* = co-first authors]