SCID MICE FOR IMMUNE THERAPY OF METASTATIC HUMAN CANCER

WE HAVE RECENTLY DEVELOPED IN NUDE MICE ORTHOPEDIC METASTASIZING ONPLANT MODELS FOR COLON, BLADDER, LUNG, HEAD AND NECK, PROSTATE, STOMACH, OVARIAN, PANCREAS AND BREAST CANCERS. WE WILL UTILIZE SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE TO DEVELOP SUBSEQUEND MODELS FOR THE DEVELOPMENT OF IMMUNOTHERAPEUTICS UTILIZING IN PART TECHNOLOGY THAT WE HAVE DEVELOPED FOR THE ONPLANT METASTASIZING OTRHOTOPIC MODELS IN NUDE MICE. TO STUDY THE FEASIBILITY OF SUCH A DEVELOPMENT IN PHASE I, WE WILL FIRST ATTEMPT TO DETERMINE THE TAKE RATE, ORTHOTOPIC GROWTH AND METASTASIZING CAPABILITY OF HUMAN COLON TUMORS ONPLANTED TO THE COLON IN SCID MICE. WE WILL THEN RECONSTITUTE THE SCID MICE WITH HUMAN PREIPHERAL LYMPHOCYTES IN VARYING AMOUNTS FROM HUMAN DONORS THAT ARE EPSTEIN-BARR VIRUS SERO-NEGATIVE. AFTER DETERMINING THE SUCCESS OF THE RECONSTITUTION, WE WILL THEN ORTHOTOPICALLY ONPLANT HUMAN COLON TUMORS AS WE DID FOR NUDE MICE AND THE UNRECONSTITUTED SCID MICE TO DETERMINE THE TAKE RATE IN THE RECONSTITUTED ACIDS AND COMPART IT WITH THE TAKE RATES IN NUDE MICE AND UNRECONSTITUTED SCIDS. IF THE TAKE RATE IS COMPARABLE IN ALL THREE MODELS, THIS WILL ALLOW, IN PHASE II, THE DEVELOPMENT OF ONPLANT ORTHOTOPIC METASTASIZING MODELS FOR THE MAJOR HUMAN CANCERS IN SCID MICE.