ENGRAFTMENT OF HUMAN TUMOR-INFILTRATING LYMPHOCYTES AND THE PRODUCTION OF ANTITUMOR ANTIBODIES IN SCID MICE

We report here that the placement of nondisrupted 1-mm(3) pieces of fr esh human lung tumor biopsy tissue into the subcutis of severe combine d immunodeficient (SCID) mice results in the engraftment of tumor-infi ltrating leukocytes (TIL) in all but 5 of 148 mice inoculated with 39 different biopsy tissue specimens, In mice coengrafted with tumor and TIL the normal histologic architecture of the tumor and TIL interface was maintained for up to 22 wk, The TIL in the xenograft were shown to divide and were maintained exclusively at the site of tumor inoculati on, It is established here that plasma cells in the TIL population pro duce Abs that react in Western blots with tumor cell lysates, These Ab s were shown to react with high and low m.w. proteins derived from bot h the membrane and cytosolic fractions of tumor cell lysates, The prod uction of human Ig was found to be T cell dependent, and immunohistoch emistry and in situ hybridization of DNA, using a human-specific cDNA probe, established the human identity of the tumor and TIL, High level s of human Ig in the sera of mice inoculated with tumor biopsy tissue are associated with the growth arrest of adenocarcinoma xenografts, Ou r results establish the co-engraftment of human tumors and TIL into SC ID mice as a new animal model with which to evaluate Ttl function and novel therapeutic strategies that are designed to augment TIL anti-tum or activity.