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In vivo administration of anti-CD3 prevents malignant progressor tumor growth
J D Ellenhorn1, R Hirsch, H Schreiber
1University of Chicago, IL 60637.
Abstract:
Malignant progressor tumors are only weakly immunogenic and can evade host recognition and rejection. One approach to therapy involves activation of the host antitumor cellular effector mechanisms. Since monoclonal antibodies to CD3 (anti-CD3) can activate T cells in vitro, an attempt was made to determine if tumor immunity could be achieved by the administration of anti-CD3 in vivo. T lymphocytes from mice injected with anti-CD3 showed increased interleukin-2 receptor (IL-2R) expression, increased proliferation to recombinant IL-2 (rIL-2), and enhanced reactivity in both an allogeneic mixed lymphocyte reaction and a mixed lymphocyte tumor culture. Malignant tumor growth in treated mice was also examined. The anti-CD3 treatment prevented tumor outgrowth that would have killed untreated animals and also stimulated an in vivo response against a malignant progressor tumor providing lasting tumor immunity.
Insights
Administering anti-CD3 monoclonal antibodies in vivo activated T cells, suppressed malignant tumor growth, and established lasting tumor immunity in mice.
Area of Science:
- Immunology
- Oncology
- Cancer Therapy
Background:
- Malignant tumors are weakly immunogenic, evading host immune responses.
- Activating host anti-tumor cellular effector mechanisms is a therapeutic strategy.
- Monoclonal antibodies to CD3 (anti-CD3) activate T cells in vitro.
Purpose of the Study:
- To determine if in vivo administration of anti-CD3 can induce tumor immunity.
- To investigate the effects of anti-CD3 on T cell activation and anti-tumor responses.
Main Methods:
- Mice were injected with anti-CD3 antibodies.
- T lymphocyte activation was assessed by IL-2 receptor expression and proliferation.
- Reactivity was measured using allogeneic mixed lymphocyte reactions and mixed lymphocyte tumor cultures.
- Tumor growth was monitored in treated and untreated mice.
Main Results:
- Anti-CD3 treatment increased T cell IL-2 receptor expression and proliferation.
- Enhanced T cell reactivity was observed in mixed lymphocyte reactions and tumor cultures.
- Anti-CD3 administration prevented tumor outgrowth in a majority of treated mice.
- Lasting tumor immunity was established against a malignant progressor tumor.
Conclusions:
- In vivo anti-CD3 administration is a viable strategy for cancer immunotherapy.
- Anti-CD3 therapy can overcome tumor immune evasion and establish long-term anti-tumor immunity.