ERADICATION OF METASTATIC TUMOR-CELLS FROM LYMPH-NODES BY LOCAL-ADMINISTRATION OF ANTI-CD3 ANTIBODY

The possibility of in vivo removal of metastatic tumour cells from lymph nodes by local intradermal administration of an anti-CD3 monoclonal antibody (mAb) was examined. Murine tumour cells in the lymph nodes were completely eradicated by intradermal injections of the mAb. This treatment was effective for removal of Lewis lung cancer cells from lymph nodes, but not for removal of subcutaneous tumours of this cell line. This treatment induced in vivo cytotoxicity in the regional lymph nodes against the syngeneic tumour cells. The following in vitro studies suggested that the cytotoxicity was probably mediated mainly by CD4+ T cells, with slight participation of CD8+ T cells. Normal lymph node and spleen cells showed cytotoxicity after in vitro incubation with the mAb for 2 days. Cell sorting with a fluorescein-activated cell sorter showed that CD4+ T cells developed during the incubation to lyse syngeneic tumor cells directly by themselves, macrophages not being involved in this tumour cell lysis. The lytic activity was detected in the cellular fractions, but not in the culture supernatants of these T cells. Furthermore, it was completely blocked by specific antiserum for tumour necrosis factor-alpha (TNFalpha). An immunoprecipitation study revealed that these T cells expressed TNFalpha molecules of 26 kDa, but not of 17 kDa, suggesting that tumour cell lysis was caused by membrane-integrated TNFalpha molecules. These results strongly suggest that local administration of anti-CD3 antibody is a very effective and appropriate procedure for eradication of metastatic tumour cells from regional lymph nodes.