Committees on Cancer Biology and Immunology and Cancer Center
Department of Pathology
The University of Chicago
5841 S. Maryland Avenue
MC 3008, Room G-305
Chicago, IL 60637
Cancer, Immunology, Pathology.
Cancer is caused by genetic mutations and immunology and genetics provide therefore most powerful tools to search for cancer-specific changes in malignant cells. Our discovery of truly cancer-specific molecular targets allow for selective immunological destruction of cancer cells without killing normal cells. Such therapies should not only be more effective but also have no noticeable side effects. Tumor-specific mutant proteins even when intranuclear can be recognized as peptides by therapeutic T cells on the surface of tumor cells. Tumor-specific mutations also affect surface structures on the cancer cells and provide cancer-specific targets for the destruction of malignant cells by therapeutic antibodies. In addition, the identification of the molecular and genetic basis of these antigens may identify critical causative mechanisms leading to cancer. Genetic manipulations of the cancer or of the surrounding host tissue ("gene therapy") can make certain cancer cells more immunogenic and/or reverse malignant growth. Activation of known oncogenes appears to be only one of the many changes required for the development of malignancy, and a cell must escape other yet unknown host control mechanisms in order to become a cancer cell.
Some of the ongoing projects in my laboratory are: 1. Identification of the genetic origins, molecular biology and function of tumor-specific antigens. 2. Development of novel strategies focusing on truly cancer-specific targets to destroy long-term established cancers. We are studying the use of recombinant high affinity T cell receptors or antibody receptors as effectors or as vehicles for molecules. Such reagents can kill the cancer cell or detect it by imaging. 3. Study of the tumor microenvironment, tumor stroma, and mechanisms of a local tumor barrier and of paracrine stimulation of tumor growth. Approaches of targeting tumor stroma and tumor vessels for destruction. 4. Mechanism of long-lasting growth arrest of cancer in the absence of T cells or antibodies by certain cytokines, tumor necrosis factor and interferon gamma in particular. 5. Development of approaches to immune prevention of cancer development in cancer-prone individuals by the deletion of initiated cells harboring oncogenes. We have generated novel transgenic models for this purpose. 6. Developing new means to prevent cancer recurrence by therapy-resistant escape variants and to eliminate residual micro-disseminated cancer cells to prevent relapse remaining in individuals following surgery, radiotherapy or chemotherapy.
Peer reviewed selected publication
Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer. Schietinger A, Arina A, Liu RB, Wells S, Huang J, Engels B, Bindokas V, Bartkowiak T, Lee D, Herrmann A, Piston DW, Pittet MJ, Lin PC, Zal T, Schreiber H. Oncoimmunology. 2013 Nov 1;2(11):e26677. Epub 2013 No 4.