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Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen
Guang-Hong Tan1, Yu-Quan Wei, Ling Tian
1Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, P R China.
Abstract:
Angiogenesis play a critical role in tumor growth and metastasis. Increasing evidence suggests that endoglin is a powerful marker of angiogenesis in solid malignancies. Thus, breaking of immune tolerance of self-endoglin-associated angiogenesis is an attractive approach to cancer therapy. To test this concept, we recombined the extracellular domains of porcine endoglin, and used it as a xenogeneic vaccine. We found that immunotherapy with porcine endoglin was effective at both protective and therapeutic anti-tumor immunity in several mouse tumor models. Autoantibodies against mouse endoglin were identified by Western blot and ELISA. IgG1 and IgG2b were substantially increased. Anti-endoglin antibody-producing B cells were detectable by ELISPOT assay. There was endothelial deposition of immunoglobulins within tumors. The anti-tumor activity was also induced by the adoptive transfer of the purified immunoglobulins. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. The increased apoptotic cells were found within the tumor tissues from the mice treated with porcine endoglin. The anti-tumor activity and production of autoantibodies against mouse endoglin could be abrogated by depletion of CD4(+) T lymphocytes. Remarkably, no marked toxicity was found in the immunized mice. These observations may provide an alternative rational strategy for active cancer immunotherapy.
Insights
Xenogeneic immunotherapy using porcine endoglin effectively targets tumor angiogenesis and growth in mouse models. This novel approach breaks immune tolerance, inducing anti-tumor immunity with minimal toxicity, offering a promising cancer therapy strategy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Angiogenesis is crucial for tumor growth and metastasis.
- Endoglin is a key marker of angiogenesis in solid tumors.
- Breaking immune tolerance to endoglin-associated angiogenesis is a potential cancer therapy.
Purpose of the Study:
- To investigate the anti-tumor efficacy of xenogeneic immunotherapy using porcine endoglin.
- To evaluate the induction of immune responses and anti-tumor activity against mouse endoglin.
Main Methods:
- Recombination of extracellular domains of porcine endoglin for xenogeneic vaccination.
- Evaluation of anti-tumor immunity in mouse models.
- Detection of autoantibodies, B cell responses, and immunoglobulin deposition.
- Assessment of angiogenesis inhibition and apoptosis induction.
- Analysis of CD4(+) T lymphocyte involvement and toxicity.
Main Results:
- Porcine endoglin immunotherapy demonstrated protective and therapeutic anti-tumor effects in mouse models.
- Autoantibodies against mouse endoglin were generated, with increased IgG1 and IgG2b levels.
- Adoptive transfer of anti-endoglin immunoglobulins mediated anti-tumor activity.
- Tumor angiogenesis was inhibited, and apoptosis was increased in treated mice.
- Anti-tumor activity was dependent on CD4(+) T lymphocytes and showed no significant toxicity.
Conclusions:
- Xenogeneic immunotherapy with porcine endoglin is a viable strategy for inducing anti-tumor immunity.
- This approach effectively inhibits tumor angiogenesis and promotes tumor cell apoptosis.
- The findings suggest a novel, safe, and rational strategy for active cancer immunotherapy.
