Eradication of metastatic tumour cells from lymph nodes by local administration of anti-CD3 antibody

Abstract

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 (TNF alpha). An immunoprecipitation study revealed that these T cells expressed TNF alpha molecules of 26 kDa, but not of 17 kDa, suggesting that tumour cell lysis was caused by membrane-integrated integrated TNF alpha 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.

Adenosine acts through an A3 receptor to prevent the induction of murine anti‐CD3‐activated killer T cells

“…6,7 Both direct cytotoxicity and indirect cytokine-related mechanisms were shown to be involved in tumor cell destruction by anti-CD3-activated killer T (AK-T) cells. 5,6,8 These encouraging results in animal models of cancer stimulated attempts to treat human cancers with AK-T cells. 9 However, although adoptive transfer of AK-T cells in combination with systemic treatment with IL-2 resulted in substantial in vivo expansion of AK-T cells and trafficking of these cells to tumor sites, there was no evidence of diminished tumor growth in cancer patients.…”

“…3,4 In addition, metastatic tumor cells were eliminated from the lymph nodes of mice after local intradermal administration of anti-CD3 MAb. 5 Adoptive immunotherapy with T cells isolated from normal spleen or tumordraining lymph nodes and activated in vitro with anti-CD3 MAb plus interleukin (IL)-2 also resulted in impressive tumor regression in syngeneic tumor-bearing mice. 6,7 Both direct cytotoxicity and indirect cytokine-related mechanisms were shown to be involved in tumor cell destruction by anti-CD3-activated killer T (AK-T) cells.…”

Syngeneic lymph-node-targeting model of green fluorescent protein-expressing Lewis lung carcinoma

“…Animals from group 1 were sacrificed 3 weeks after tumor cell injection (mouse numbers [11][12][13][14][15][16][17][18][19][20]. The rest of the animals were sacrificed 5 weeks after the tumor cell injection (group 2: mouse numbers 1-10).…”

Further characterization of cytotoxic T cells generated by short-term culture of human peripheral blood lymphocytes with interleukin-2 and anti-CD3 mAb

“…In view of the important secretion of cytokines (including IL-2) induced by these antibodies [11,17,19,51] it was proposed that anti-CD3 mAb could participate in the induction of a non-MHC-restricted LAK-like cytotoxic activity by T cells [12]. Recently, two groups [16,43] have demonstrated the induction of antitumor activity using anti-CD3 mAb, in an in vivo murine model. In these studies, the injection of anti-CD3 [16] alone or in combination with IL-2 [43] in tumor-bearing mice induced the reduction [43] or the eradication [16] of tumor metastasis.…”

“…Recently, two groups [16,43] have demonstrated the induction of antitumor activity using anti-CD3 mAb, in an in vivo murine model. In these studies, the injection of anti-CD3 [16] alone or in combination with IL-2 [43] in tumor-bearing mice induced the reduction [43] or the eradication [16] of tumor metastasis. However, very few studies carefully evaluated the antitumoral activity of T cells stimulated by anti-CD3 mAb with sorted lymphocyte subsets, most likely because classical sorting procedures are laborious and interfere with the function of cytotoxic effectors.…”