Version 2.1.1.0

Abstract

Grant Number:	1R43CA101287-01
PI Name:	RANKIN, CHRISTOPHER T.
PI Email:	rankinc@macrogenics.com
PI Title:
Project Title:	Superantigens in Epstein-Barr Virus Pathology

Abstract: DESCRIPTION (provided by applicant): Superantigens (SAG) are believed to contribute to the pathogenesis of certain infectious agents by activating a broad subset of primary T-cells. Through association with MHC class II molecules outside of the peptide recognition cleft, the SAG is able to bind and activate T-cells expressing a particular T-cell receptor (TCR) beta chain variable gene. Recent experiments have identified a SAG, encoded by the human endogenous retrovirus K18 env (HK18 env) gene, which is transcriptionally activated following infection with the Epstein-Barr virus (EBV). EBV is a ubiquitous, B-cell tropic herpesvirus, which has been identified as a causative agent for infectious mononucleosis (IM), a self-limiting lymphoproliferative disorder characterized by mononuclear leukocytosis. The association of EBV and a SAG activity provides an attractive hypothesis for the mechanism of EBV related T-cell proliferation. However, the exact role of the SAG in EBV infection and pathology is not currently known. The goal of this phase I application is to evaluate the role of the recently identified SAG molecule, HERV-K18 Env, in EBV infection and pathology. Our working hypothesis is that SAG activated T-cells supply an essential component necessary for the development of EBV associated B-cell lymphomas. Thus, blocking T-cell activation by the SAG could effectively prevent the development of EBV tumors. If this hypothesis is correct, these studies will provide a basis for phase II studies in primate models of EBV infection, in order to examine the potential for anti-SAG antibodies as preventative or therapeutic agents against EBV related disease.

Thesaurus Terms:
Epstein Barr virus, T lymphocyte, carcinogenesis inhibitor, immunologic substance development /preparation, leukocyte activation /transformation, monoclonal antibody, superantigen, virus related neoplasm /cancer
lymphoma, passive immunization, virus envelope
clinical research, human subject, laboratory mouse

Institution:	MACROGENICS, INC.
	1500 E GUDE DR, STE B
	ROCKVILLE, MD 20850
Fiscal Year:	2003
Department:
Project Start:	06-JUN-2003
Project End:	31-MAY-2004
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZRG1

---