Activation of human lymphocytes by a monoclonal antibody to B lymphoblastoid cells; molecular mass and distribution of binding protein

Abstract

A novel monoclonal antibody (BAT) to the B-lymphoblastoid cell line activates murine lymphocytes and exhibits a striking antitumor activity in mice. In order to evaluate the potential use of this antibody against human cancer, we have investigated its immuno-stimulatory properties on human peripheral blood lymphocytes (PBL). Our findings demonstrate that BAT mAb induces proliferation and cytotoxicity in human PBL against natural-killer-cell-sensitive and natural-killer-cell-resistant tumor cell lines. Interleukin-2 at a low concentration synergizes with BAT mAb in eliciting these effects. BAT mAb binds to human peripheral T cells as revealed by a double-labelling technique using anti-CD3 and BAT mAb. The molecular mass of the antigen recognized by BAT mAb was 48-50 kDa under reducing and non-reducing conditions. This study provides a basis for future experiments to evaluate the use of BAT mAb in the immunotherapy of cancer.

A lymphocyte-activating monoclonal antibody induces regression of human tumors in severe combined immunodeficient mice

“…Inoculation i.v. of human SK28 melanoma cells led to development of tumor lesions in the lungs (similar to the previously reported model of established lung metastases using a variety of syngeneic murine tumors) (14). Administration of BAT to these mice, 14 days after tumor inoculation, resulted in a marked regression of tumor lesions in the lungs (Table 4, Fig.…”

“…We then established that engraftment of murine splenocytes enabled BAT to induce regression of murine B16 melanoma in the SCID mice (Table 3). BAT was administered 14 days posttumor inoculation, the time at which BAT was previously found to be most effective in inducing regression of murine tumors in wild-type mice (14). BAT treatment in the engrafted SCID mice reduced the number of lung metastases from 217 Ϯ 65 to an average of only 7 Ϯ 3.…”

“…BAT was generated and purified as described (14). In brief, BALB͞c mice were immunized with membranes from Daudi cells.…”

“…We previously reported a mAb directed against human B-lymphoblastoid cell membranes (BAT) that stimulates human lymphocytes, as manifested by enhanced murine and human lymphocyte proliferation and cytolytic activity against tumor cells in vitro (13). BAT binding protein was identified as a 48-to 50-kDa monomeric protein (13).…”

“…BAT binding protein was identified as a 48-to 50-kDa monomeric protein (13). BAT was found to induce murine tumor regression in C57BL mice that was mediated by its immune stimulatory properties (14).…”