MONOCLONAL ANTIBODIES TO COMMON TUMOR IDIOTOPES FOR TH THERAPY OF B-CELL NEOPLASMS

THE MAIN OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP EFFICACIOUS IMMUNOTHERAPY FOR HUMAN B CELL NEOPLASMS EMPLOYING ANTI-IDIOTYPE (ANTI-ID) MONOCLONAL ANTIBODIES (MOABS). THE SPECIFIC AIMS OF THIS PHASE I PROPOSAL ARE TO DEVELOP ANTI-ID MOABS TO LYMPHOMA AND CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) CROSS-REACTIVE IDIOTOPES. THE AVAILABILITY OF A PANEL OF MOABS TO COMMON TUMOR IDIOTOPES SUITABLE FOR THE TREATMENT OF MULTIPLE PATIENTS WOULD GREATLY ENHANCE THEPRACTICALITY OF ANTI-ID THERAPY. ANTICOMMON ID MOABS WITH THE HIGHEST FREQUENCY OF TUMOR CROSS-REACTIVITY AND WITH ACCEPTABLE CORRESPONDING SERUM IDIOTOPE LEVELS (<50 UG/ML) WILL BE CHOSEN FOR FUTURE USE IN HUMAN CLINICAL TRIALS DURING THE PHASE 2 PERIOD. THESE CLINICAL STUDIES WILL EMPLOY A MULTI-MODALITY APPROACH INCORPORATING ANTI-ID MOABS CONJUGATED TO CYTOTOXIC RADIOISOTOPES OR ADMINISTERED IN CONJUNCTION WITH OTHER BIOLOGICAL RESPONSE MODIFIERS. OVERALL, THE RESULTS OF THE PHASE 1 AND 2 STUDIES SHOULD LEAD TO THE PRACTICAL DEVELOPMENT OF ANTI-ID MOAB IMMUNOTHERAPIES WHICH MAY FIND FUTURE APPLICATION IN THE TREATMENT OF HUMAN B CELL LYMPHOMA AND CLL.