Hans Schreiber, M.D., Ph.D.

Tumor Immunology; Tumor Progression, Tumor-Specific T-cell Clones; Characterization of Tumor Variants; Molecular Genetics of Tumor Antigens

Research Summary

The main focus of this laboratory is to study the fundamental mechanisms that govern the interaction of cancer cells with the immune system. In particular, our laboratory is trying to exploit the fact that cancer cells usually carry cancer-specific mutations and antigens, and that, under certain conditions, the immune system can destroy cancer cells even after they have disseminated in the body. We are trying to understand the mechanisms that often allow immunogenic cancer cells to escape immune destruction, and we want to develop new strategies and principles on which to base novel therapeutic approaches. We are also studying the signals needed for the immune system to be alerted by cancer cells, and then to destroy these cells. For these studies we are using newest molecular tools and novel bio-engineered molecules and technologies. Finally, we combine immunology with genetics and biochemistry, a combination that provides a most powerful tool to search for cancer-specific changes in malignant cells. Identification of these changes may not only identify critical causative mechanisms but also new immunological and pharmacological targets that can be used to destroy the cancer.

Some of the ongoing projects in my laboratory are:

1. Mechanism of tumor escape from host immunity. Development of new strategies to prevent this escape by genetic engineering and immune manipulations.

2. Mechanisms leading to paracrine stimulation of tumor growth. Novel
approaches of using tumor stroma as therapeutic target.

3. Use of tumor-specific mutant proteins or viral oncoproteins (E6/E7 of HPV) as target for immune prevention of primary cancer development.

4. Identification of the molecular basis and genetic origins of tumor-specific target antigens and target molecules that cannot be lost by cancer cells.

Selected Papers

Monach PA, Meredith SC, Siegel CT and Schreiber H. (1995). A unique tumor antigen produced by a single amino acid substitution. Immunity, 2:45-59.

Dubey P, Hendrickson RC, Meredith SC, Siegel CT, Shabanowitz J, Skipper JCA, Engelhard VH, Hunt DF and Schreiber H. (1997). The immunodominant antigen of a UV-induced regressor tumor is generated by a tumor-specific somatic point mutation in a dead-box protein. J. Exp. Med. 185:695-705.

Wick M, Dubey P, Koeppen H, Siegel CT, Fields PE, Chen L, Bluestone JA and Schreiber H. (1997). Antigenic cancer cell grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy. J. Exp. Med. 186: 229-238.

Mumberg D, Monach PA, Wanderling S, Philip M, Toledano AY, Schreiber RD, Schreiber H. (1999). CD4+ T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-g. Proc. Natl. Acad. Sci. USA, 96:8633-8638.

Siegel CT, Schreiber K, Meredith SC, Beck-Engeser G, Lancki DW, Lazarski CA, Fu Y, Rowley DA and Schreiber H. (2000). 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.

Beck-Engeser GB, Monach PA, Mumberg D, Yang F, Wanderling S, Schreiber K, Espinosa R III, Le Beau MM, Meredith SC and Schreiber H.  (2001). 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.

Spiotto M, Yu P, Rowley DA, Nishimura MI, Meredith SC, Gajewski TG, Fu YX and Schreiber H. (2002). Increasing tumor antigen expression overcomes ignorance to solid tumors via cross-presentation by bone marrow-derived stromal cells. Immunity 17:737-747.