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

Monoclonal antibodies were raised against Daudi B-lymphoblastoid cell line membranes. An mAb (BAT) was selected for its ability to stimulate human and murine lymphocyte proliferation. BAT induced cytotoxicity in human and murine lymphocytes against natural killer cell-sensitive and -resistant tumor cell lines. A single intravenous administration of BAT to mice that had been inoculated with various murine tumors (e.g., B16 melanoma, 3LL carcinoma, and methylcholanthrene fibrosarcoma) resulted in striking antitumor effects as manifested by complete tumor regression and prolonged survival of the treated mice. BAT exhibited a diminished but significant antitumor effect in athymic nude mice, which are deficient in T lymphocytes, and in beige mice, which are deficient in NK cells. Furthermore, selective depletion of T or NK cells in mice reduced the response to the antitumor effect of BAT. These data indicate a dual role for T and NK cells in mediating the antitumor activity of BAT. We report here on the antitumor activity of BAT mAb on human tumor xenografts in mice. BAT demonstrated an antitumor effect in nude mice bearing human colon carcinoma (HT29) xenografts. It failed, however, to inhibit established lung metastases in severe combined immunodeficient (SCID) mice that had been inoculated (i.v.) with SK28 human melanoma. Engraftment of human lymphocytes into SCID mice bearing human melanoma xenografts rendered them responsive to the antitumor effect of BAT. The efficacy of BAT in the regression of human tumors by activation of human lymphocytes indicates its potential clinical use.

Immune stimulatory and anti-tumor properties of anti-CD3 and BAT monoclonal antibodies: a comparative study.

A novel monoclonal antibody raised to Daudi cell membranes was found to exhibit immune stimulatory and anti-tumor properties. The activity of this antibody (BAT) which also binds T cells was compared to that of anti-CD3. Anti-CD3 reacts with the T cell receptor complex, induces cell proliferation, and cytolytic activity in vitro and also manifests in vivo anti-tumor effect against murine tumors. Comparison of the two antibodies demonstrates similar induction in vitro of splenocyte proliferation and cytolytic activity. Both BAT and anti-CD3 antibodies manifest anti-tumor activity in mice bearing B16 melanoma. They differ however in the timing of antibody administration post-tumor inoculation which is most effective in eliciting the anti-tumor effect. Whereas BAT is most effective when administered 10 to 14 days post-tumor inoculation, anti-CD3 is effective at an early time. Data also indicate that BAT synergises with tumor cells in eliciting cell proliferation in vitro. In contrast, this effect could not be demonstrated with anti-CD3. The properties of BAT may be of advantage in its potential clinical use.

A monoclonal antibody against a human B lymphoblastoid cell line induces tumor regression in mice.

We have developed a monoclonal antibody (BAT) to Daudi B lymphoblastoid cell line membranes. The antibody was selected for its ability to stimulate lymphocyte proliferation. Splenocytes of BALB/c or C57BL mice given i.v. injections of 10 micrograms/mouse of BAT exhibited increased proliferation and cytotoxic activity. A single i.v. administration of BAT monoclonal antibody 2 weeks after B16 melanoma cell inoculation resulted in a striking antitumor effect as manifested by the elimination of lung metastases and prolonged survival of the treated mice. BAT monoclonal antibody was also effective in the regression of tumors in mice bearing 3LL (Lewis lung carcinoma) and MCA-105 (fibrosarcoma). Transfer of 10(7)-10(8) splenocytes from mice that had been given injections of BAT to B16- or 3LL-inoculated recipients led to a reduction of lung metastases. Splenocytes from B16-inoculated mice that were cured by BAT were more effective than those from mice treated with BAT alone against recipients bearing either B16 or 3LL tumors. The antitumor activity of BAT is related to its immunostimulatory properties.