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Targeting of anti-tumor responses with bispecific antibodies
D M Segal1, J H Qian, D Mezzanzanica
1Experimental Immunology Branch, National Institutes of Health, Bethesda, MD 20892.
Abstract:
T cells can be induced to specifically lyse tumor cells with bispecific antibodies containing anti-T cell receptor mAbs crosslinked to anti-tumor mAbs. Such "targeted cytolysis" requires that the target cell be bound directly to the cytotoxic cell. In addition, targeted T cells mediate a second activity, the secretion of factors that can block the growth of both tumor target cells and bystander tumor cells. When given to nude mice bearing intraperitoneal human ovarian carcinoma, targeted human T cells cause the rapid removal of most tumor cells from the peritoneum, and markedly prolong the times of survival of treated mice. The efficacy of targeted T cells for treating human cancer is currently being tested in clinical trials.
Insights
Bispecific antibodies enable T cells to target and destroy tumor cells, also secreting factors that inhibit tumor growth. This approach shows promise in treating ovarian cancer in mice and is under clinical investigation.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- T cells are crucial for immune responses.
- Cancer immunotherapy aims to harness the immune system to fight cancer.
- Bispecific antibodies offer a strategy to redirect T cell activity against cancer cells.
Purpose of the Study:
- To investigate the efficacy of T cells engineered with bispecific antibodies for targeted cancer cell lysis.
- To evaluate the potential of these engineered T cells to inhibit tumor growth and improve survival in a preclinical cancer model.
Main Methods:
- Bispecific antibodies were used to crosslink anti-T cell receptor monoclonal antibodies (mAbs) with anti-tumor mAbs.
- Targeted cytolysis assay was performed to assess direct tumor cell killing.
- In vivo studies involved administering targeted human T cells to nude mice with human ovarian carcinoma.
Main Results:
- Targeted T cells demonstrated specific lysis of tumor cells through direct binding.
- Engineered T cells secreted factors that inhibited the growth of both target and bystander tumor cells.
- Treatment of mice with ovarian carcinoma led to rapid tumor cell clearance and significantly prolonged survival.
Conclusions:
- Targeted T cells mediated by bispecific antibodies are effective in eliminating tumors and improving survival in a preclinical model.
- This approach, termed 'targeted cytolysis,' represents a promising strategy for cancer treatment.
- The efficacy of targeted T cells is currently being evaluated in human clinical trials for cancer therapy.