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Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Protective antitumor immunity induced by immunization with completely allogeneic tumor cells
R E Toes1, R J Blom, E van der Voort
1Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
Immunizing mice with allogeneic tumor cells engineered with adenovirus type 5 early region 1 (Ad5E1) successfully generated a strong anti-tumor immune response. This approach induced protective immunity against syngeneic tumors, highlighting potential for allogeneic tumor cell vaccines.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Previous studies demonstrated that immunization with syngeneic adenovirus type 5 early region 1 (Ad5E1)-transformed tumor cells induces a specific cytotoxic T lymphocyte (CTL) response.
- The H-2Db-restricted CTL response targets an E1B-encoded CTL epitope.
Purpose of the Study:
- To investigate the efficacy of using completely allogeneic tumor cells, engineered with Ad5E1, for inducing anti-tumor immunity.
- To determine if an allogeneic response would impede the induction of a specific anti-tumor CTL response.
Main Methods:
- Mice were immunized with Ad5E1-transformed tumor cells from a different genetic strain (BALB/c, H-2d) than the host (B6, H-2b).
- CTL responses were analyzed, focusing on the recognition of E1B-encoded epitopes presented by H-2Db.
- Mice were subsequently challenged with syngeneic B6 Ad5E1-expressing tumor cells to assess protective immunity.
Main Results:
- Immunization with allogeneic Ad5E1-transformed tumor cells induced a robust CTL response against the E1B-encoded epitope presented by H-2Db.
- The induction of a B6 anti-BALB/c allo-response did not inhibit the development of the anti-E1B CTL response.
- Mice vaccinated with allogeneic Ad5E1 cells were protected against a challenge with syngeneic B6 Ad5E1-expressing tumor cells, unlike those vaccinated with untransformed allogeneic cells.
Conclusions:
- Immunization with completely allogeneic tumor cells engineered with Ad5E1 can effectively induce protective syngeneic anti-tumor immunity.
- Allogeneic tumor cell vaccines are a viable strategy for inducing anti-tumor immunity, overcoming potential overwhelming allogeneic responses.
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