METAMOUSE FOR DIAGNOSTIC AND THERAPEUTIC TUMOR MARKERS

A NUMBER OF MONOCLONAL ANTIBODIES (MABS) SPECIFIC FOR TUMOR-ASSOCIATED ANTIGENS HAVE BEEN ANALYZED FOR IMMUNOLOCALIZATION AND/OR TUMOR-GROWTH INHIBITION IN ATHYMIC MICE BEARING SUBCUTANEOUSLY TRANSPLANTED HUMAN XENOGRAFTS DERIVED FROM TUMOR CELL LINES. ALTHOUGH THE SUBCUTANEOUS-TRANSPLANT NUDE-MOUSE MODEL IS WELL ACCEPTED FOR THE IN VIVO EVALUATION OF MAB-TARGETING, SOME NEGATIVE ASPECTS NEED TO BE CONSIDERED: THE ANTIGENIC HETEROGENEITY OF HUMAN SOLID TUMORS AND THE DIFFICULTY OF STUDYING DISTANT METASTASES. THEREFORE, IT WOULD BE EXTREMELY IMPORTANT TO HAVE AN ANIMAL MODEL IN WHICH TO SCREEN NOT ONLY THE REACTIVITY OF A GIVEN MAB BUT, MOST IMPORTANTLY, TO TEST PRECLINICALLY THE SPECIFIC PATIENT-REACTIVITY OF A GIVEN MAB IN THE PRIMARY TUMOR AND INT THE METASTASES AND, THEREFORE, INDIVIDUALIZE PATIENT TREATMENT. THE METAMOUSE MODEL DEVELOPED BY US FOR A NUMBER OF DIFFERENT HUMAN CANCERS (PROC. NATL. ACAD. SCI. 88, 9345-9349, 1991; AND INT. J. CANCER 49, 938-939, 1991) ALLOWS LOCAL GROWTH AND METASTASES IN NUDE MICE AFTER ORTHOTOPIC TRANSPLANTATION OF HUMAN TUMOR SURGICAL SPECIMENS. THUS, THIS MODEL GIVES US THE POSSIBILITY OF STUDYING THE ABILITY OF A GIVEN MAB TO TARGET, BOTH THE PRIMARY TUMOR (LOCALLY GORWING) AND DISTANT METASTASES. THE CONCOMITANT USE OF AN IN VITRO TEST TO SCREEN THE REACTIVITY OF THE MAB ON LIVING TUMOR TISSUES GROWING IN A SPONGE-GEL-SUPPORTED 3-DIMENSIONAL CULTURE (IN VITRO CELL. DEV BIO. 28A,297-299, 1992) ALLOWS THE DETERMINATION OF THE POTENTIAL TARGETING ABILITY OF THE ANTIBODY USED ON THE SPECIFIC TISSUE TESTED. WE PLAN TO STUDY THE RADIOLOCALIZATION OF MABS (SUCH AS B72.3, CC49 AND COL-1) IN THIS NEW ANIMAL MODEL COMPARING THE RESULTS TO THOSE OBTAINED IN VITRO, TO EVALUATE THE POSSIBILITY OF OBTAINING PRECLINICAL MODELS IN WHICH TO DEVELOP AND EVALUATE INDIVIDUALIZED MAB-BASED THERAPY.