University of Chicago :: Department of Pathology ::

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Hans Schreiber, MD, DMSc. PhD

Professor
Committees on Cancer Biology and Immunology and Cancer Center

Contact

The University of Chicago
5841 S. Maryland, MC 3008
Chicago, IL 60637-1470
Phone: (773) 702-9204
Fax: (773) 702-9224
hszz@midway.uchicago.edu

Committee Membership

Committee on Cancer Biology
Committee on Immunology
Cancer Research Center

Honors

Studienstiftung des Deutschen Volkes
Goedecke Prize
Merit Award
Alexander-von-Humboldt Prize

Clinical Interest

Cancer, Immunology, Pathology

Research Interests

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.

Selected Publications

Schietinger A, Philip M, Yoshida BA, Azadi P, Liu H, Meredith SC, Schreiber H. A mutant chaperone converts a wild-type protein into a tumor-specific antigen. Science. 314: 304-8, 2006.
Schreiber K, Rowley DA, Riethmuller G, Schreiber H. Cancer immunotherapy and preclinical studies: why we are not wasting our time with animal experiments. Hematol Oncol Clin North Am. 20:567-84, 2006.
Spiotto MT, Rowley DA, and Schreiber H. “Bystander” elimination of antigen loss variants in established tumors. Nature Medicine 10: 294-8, 2004.
Schreiber H. Tumor Immunology. Chapter 48. In: Fundamental Immunology 5th edition. W.E. Paul, ed. Lippincott Raven Press, New York pp 1557-1592, 2003
Spiotto MT, Yu P, Rowley DA, Nishimura MI, Meredith SC, Gajewski TF Y.X. Fu YX, and Schreiber H. Increasing tumor antigen expression overcomes "ignorance" to solid tumors via crosspresentation by bone marrow-derived stromal cells. Immunity 17:737-747, 2002.
Beck-Engeser GB, Monach PA, Mumberg D, Yang F, Wanderling S, Schreiber K, Espinosa R, LeBeau M, Meredith SC, and Schreiber H. Point mutation in essential genes with loss or mutation of the second allele: Relevance to the retention of tumor-specific antigens. J. Exp. Med. 194:285-300, 2001.
Siegel CT, Schreiber K, Meredith SC, Beck-Engeser G, Lanck, DW, Lazarski CA, Fu Y, Rowley DA, and Schreiber H. Enhanced growth of primary tumors in cancer-prone mice following immunization against the mutant region of an inherited oncoprotein. J. Exp. Med., 191:1945-56, 2000.
Mumberg D, Monach PA, Wanderling S, Philip M, Toledano AY, Schreiber RD, Schreiber H. CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc. Natl. Acad. Sci. USA, 96:8633-8638, 1999.
Wick M, Dubey P, Koeppen H, Siegel CT, Fields PE, Fitch FW, Chen L, Bluestone JA and Schreiber H.. Antigenic cancer cells can grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy. J. Exp. Med., 185:229-237, 1997.
Dubey P, Hendrickson RC, Meredith SC, Siegel CT, Shabanowitz J, Skipper JCA, Engelhard VH, Hunt DF and Schreiber H.: The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD box helicase p68. J. Exp. Med.,185:695-705, 1997.
Monach PA, Meredith SC, Siegel CT and Schreiber H. A unique tumor antigen produced by a single amino acid substitution. Immunity, 2:45-59, 1995.
Wortzel RD, Philipps C and Schreiber H. Multiplicity of unique tumor-specific antigens expressed on a single malignant cell. Nature 304:165-167, 1983.

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