Olivera J. Finn, Ph.D.
Campus: The Assembly, 5051 Centre Ave
Pittsburgh, PA 15213
- Ph.D. - Stanford University (1980)
- Postdoc - Stanford University (1980-1982)
- Distinguished Professor, Department of Immunology
- Distinguished Professor, Department of Surgery
The long-standing interests of our laboratory center on identifying specific mechanisms of human anti-tumor immunity and cancer immunosurveillance. We study T cell and antibody repertoire in cancer patients and in healthy individuals at risk for cancer and factors that influence that repertoire. We were the first to identify a human tumor antigen recognized by human T cells and antibodies, the epithelial mucin MUC1. We showed that tumors express an abnormal form of MUC1 that is recognized by the immune system as a foreign rather than a self-antigen. Studies in mice and primates showed that MUC1 was immunogenic and that anti-MUC1 immune responses can reject tumors. These studies supported multiple clinical trials of a MUC1 vaccine in patients with breast, colon and pancreatic cancer. Most recently, we began testing a MUC1 vaccine for cancer prevention in individuals diagnosed with MUC1+ premalignant lesions. In addition to being a tumor antigen, MUC1 is an oncogene by virtue of promoting a highly inflammatory tumor microenvironment. We discovered that the tumor form of MUC1 activates NF-kB, binds p65 and translocates to the tumor cell nucleus where it binds to and activates promoters of inflammatory cytokines, such as IL-6 and TNF-a. MUC1 has been associated with a more invasive cancer phenotype and we have recently deciphered the mechanism by showing that it forms complexes with CIN-85, also previously associated with cell motility and invasion.
While studying MUC1 and another tumor antigen that we discovered, cyclin B1, we made an important observation that many tumor associated antigens (TAA) described by their abnormal expression on cancer cells, are also abnormally expressed in other acute or chronic inflammatory conditions and are therefore more appropriately defined as disease associated antigens (DAA). These include bacterial infections such as Mumps, viral infections such as chicken pox, and chronic inflammations such as inflammatory bowel disease (IBD). This observation helped us formulate and test a new hypothesis on cancer immunosurveillance. Working in collaboration with epidemiologists and creating appropriate mouse models, we showed that immunity to abnormal self-antigens, DAAs, is generated simultaneously with immunity to pathogens early in life in the course of febrile infections. Immune memory for DAAs contributes to effective immunosurveillance of other pathogen infections throughout life, as well as of cancer that expresses many of those same antigens. Lastly, we are pursuing an idea that the quantity and the quality of immune memory for DAAs is critical for maintaining general immune health. Using genomic and bioinformatics approaches, we are defining a gene expression signature that characterizes individuals with strong immunosurveillance ability versus those that lack that ability and designing DAA-based vaccines to promote immunosurveillance of cancer and other diseases.
Jacqueline C, Dracz M, Boothman S, Minden JS, Gottschalk RA, Finn OJ. Identification of Cell Surface Molecules That Determine the Macrophage Activation Threshold Associated With an Early Stage of Malignant Transformation. Front Immunol. 2021 Oct 12;12:749597. doi: 10.3389/fimmu.2021.749597. PMID: 34712237; PMCID: PMC8546176.
Jacqueline C, Lee A, Frey N, Minden JS, Finn OJ. Inflammation-Induced Abnormal Expression of Self-molecules on Epithelial Cells: Targets for Tumor Immunoprevention. Cancer Immunol Res. 2020 Aug;8(8):1027-1038. doi: 10.1158/2326-6066.CIR-19-0870. Epub 2020 May 28. PMID: 32467324; PMCID: PMC7415557.
Miller ML, Finn OJ. Flow cytometry-based assessment of direct-targeting anti-cancer antibody immune effector functions. Methods Enzymol. 2020;632:431-456. doi: 10.1016/bs.mie.2019.07.026. Epub 2019 Aug 12. PMID: 32000909; PMCID: PMC7000137.
Ma P, Beatty PL, McKolanis J, Brand R, Schoen RE, Finn OJ. Circulating Myeloid Derived Suppressor Cells (MDSC) That Accumulate in Premalignancy Share Phenotypic and Functional Characteristics With MDSC in Cancer. Front Immunol. 2019 Jun 19;10:1401. doi: 10.3389/fimmu.2019.01401. PMID: 31275327; PMCID: PMC6594197.
Finn OJ. The dawn of vaccines for cancer prevention. Nat Rev Immunol. 2018 Mar;18(3):183-194. doi: 10.1038/nri.2017.140. Epub 2017 Dec 27. PMID: 29279613.
Finn OJ. Human Tumor Antigens Yesterday, Today, and Tomorrow. Cancer Immunol Res. 2017 May;5(5):347-354. doi: 10.1158/2326-6066.CIR-17-0112. PMID: 28465452; PMCID: PMC5490447.
Finn OJ. A Believer's Overview of Cancer Immunosurveillance and Immunotherapy. J Immunol. 2018 Jan 15;200(2):385-391. doi: 10.4049/jimmunol.1701302. PMID: 29311379; PMCID: PMC5763509.
Lohmueller JJ, Ham JD, Kvorjak M, Finn OJ. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. Oncoimmunology. 2017 Oct 26;7(1):e1368604. doi: 10.1080/2162402X.2017.1368604. PMID: 29296519; PMCID: PMC5739565.