METHODS ARE NOW AVAILABLE FOR IDENTIFYING AND PURIFYING A VAST ARRAY OF ANTIGENS EXPRESSED ON TUMOR CELLS.

METHODS ARE NOW AVAILABLE FOR IDENTIFYING AND PURIFYING A VAST ARRAY OF ANTIGENS EXPRESSED ON TUMOR CELLS. THE PURPOSE OF THE PROPOSED STUDIES IS TO DEVELOP METHODS FOR SENSITIZING T CELLS TO ANTIGENS THAT CAN BE PURIFIED FROM TUMOR CELL MEMBRANES, RATHER THAN SENSITIZING WITH INTACT TUMOR CELLS EXPRESSING THE ANTIGEN. PHASE I STUDIES WILL UTILIZE A MURINE TUMOR EXPRESSING A WELL-DEFINED TUMOR ASSOCIATED ANTIGEN (TAA), WHICH CAN BE READILY PURIFIED AND IS KNOWN TO ELICIT A MEASURABLE T-CELL RESPONSE. THESE STUDIES SHOULD PROVIDE INSIGHT INTO HOW TO HANDLE TAA SO AS TO RETAIN IMMUNOGENICITY AND TO PERMIT GENERATION OF BOTH CYTOTOXIC EFFECTOR T CELLS AND HELPER/DTH EFFECTOR T CELLS REACTIVE WITH THE TUMOR. STUDIES PERFORMED WITH BIOCHEMICALLY PROCESSED TAA AND BIOSYNTHETIC PLANAR LIPID MEMBRANES AS AN ANTIGEN-PRESENTING SURFACE SHOULD HELP DEVELOP METHODOLOGY FOR BYPASSING THE REQUIREMENT FOR BOTH INTACT TUMOR CELLS AND ANTIGEN-PRESENTING CELLS FROM THE PATIENT FOR IN VITRO SENSITIZATION OF T CELLS. MOREOVER, THIS TECHNOLOGY MAY PERMIT DEVELOPMENT OF HIGHLY IMMUNOGENIC SENSITIZING SURFACES, SINCE THE ARTIFICIAL MEMBRANES CAN BE MADE TO EXPRESS MUCH HIGHER DENSITY TAA THAN THE INTACT TUMOR CELL. PHASE II STUDIES WILL USE THESE METHODS TO DETERMINE WHETHER HUMAN TAA PURIFIED FROM SQUAMOUS CARCINOMA CELLS, USING MONOCLONAL ANTIBODIES THAT HAVE BEEN GENERATED AND CHARACTERIZED AT INTEK DIAGNOSTICS, CAN BE USED TO STIMULATE REACTIVE T CELLS FROM PATIENTS.