HU/SCID MOUSE MODEL: PREDICTING IMMUNOTHERAPY RESPONSES

ACTIVE IMMUNOTHERAPY USING ANTI-IDIOTYPIC ANTIBODIES THAT MIMIC TUMOR-ASSOCIATED ANTIGENS HAS BEEN SHOWN TO BE EFFECTIVE IN ANIMALS AND HUMAN PATIENTS. THIS RESEARCH IS AIMED AT OPTIMIZING THE CLINICAL RESPONSE OF MALIGNANT MELANOMA PATIENTS TO ANTI-IDIOTYPE IMMUNOTHERAPY CURRENTLY UNDER DEVELOPMENT. THIS WILL BE ACHIEVED BY IDIOTYPE MATCHING A THERAPEUTIC ANTIBODY FROM A PANEL OF ANTI-IDIOTYPIC ANTIBODIES WITH THE INDIVIDUAL IDIOTYPIC REPERTOIRE OF THE PATIENT. AN ASSAY THAT QUANTITATIVELY DETERMINES THE FREQUENCY OF IDIOTYPE-RESPONSIVE B AND T CELLS IN PROSPECTIVE IDIOTYPE THERAPY PATIENTS WILL BE DEVELOPED. SCID MICE WILL BE RECONSTITUTED WITH THE PERIPHERAL BLOOD LYMPHOCYTES FROM MELANOMA PATIENTS. THE SPLENIC FOCUS ASSAY WILL THEN BE USED TO DETERMINE THE FREQUENCY OF LYMPHOCYTES RESPONSIVE TO ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES. FURTHERMORE, THIS SCID SPLENIC FOCUS ASSAY WILL MAKE IT POSSIBLE TO ANALYZE THE PATIENT'S T-CELL REPERTOIRE WITH RESPECT TO T-HELPER-CELL RESPONSES.