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 lym ph nodes by local intradermal administration of an anti-CD3 monoclonal antibody (mAb) was examined. Murine tumour cells in the lymph nodes w ere completely eradicated by intradermal injections of the mAb. This t reatment was effective for removal of Lewis lung cancer cells from lym ph nodes, but not for removal of subcutaneous tumours of this cell lin e. This treatment induced in vivo cytotoxicity in the regional lymph n odes against the syngeneic tumour cells. The following in vitro studie s 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 t he mAb for 2 days. Cell sorting with a fluorescein-activated cell sort er showed that CD4+ T cells developed during the incubation to lyse sy ngeneic tumor cells directly by themselves, macrophages not being invo lved in this tumour cell lysis. The lytic activity was detected in the cellular fractions, but not in the culture supernatants of these T ce lls. 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, bu t not of 17 kDa, suggesting that tumour cell lysis was caused by membr ane-integrated TNFalpha molecules. These results strongly suggest that local administration of anti-CD3 antibody is a very effective and app ropriate procedure for eradication of metastatic tumour cells from reg ional lymph nodes.