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Updated: Oct 9, 2026

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
Published on: August 13, 2013
An adenovirus type 5 early region 1B-encoded CTL epitope-mediating tumor eradication by CTL clones is down-modulated
R E Toes1, R Offringa, R J Blom
1Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
Abstract:
Mouse embryo cells (C57BL/6, H-2b) transformed by the E1A and E1B genes of adenovirus type 5 (Ad5E1 MEC) are highly immunogenic. Previously, CTL were cloned from mice immunized with Ad5E1 MEC. These CTL clones were capable of tumor eradication in nude mice, and were directed against the Ad5E1A-encoded decapeptide SGPSNTPPEI, presented by the H-2Db MHC molecule. We have now generated Ad5E1 MEC containing a mutated Ad5E1A-encoded epitope. The mutant Ad5E1 MEC induce a strong CTL response when injected into immunocompetent mice. CTL clones generated against mutant Ad5E1-transformed tumor cells recognize an Ad5E1B-encoded epitope (VNIRNCCYI) in the context of H-2Db. Because this epitope is also present on wild-type Ad5E1 MEC, it is concluded that Ad5E1-transformed tumor cells express at least two CTL epitopes. Interestingly, the lysis of Ad5E1 MEC by the Ad5E1B-specific, but not by the Ad5E1A-specific, CTL clones was strongly diminished by the action of the activated ras oncogene. CTL directed against the Ad5E1B-encoded epitope were, like Ad5E1A-specific CTL, able to eradicate large established Ad5E1-induced tumors in B6 nude mice, demonstrating that CTL activity directed against different CTL epitopes expressed by the same tumor can be exploited for immunotherapy of cancer.
Insights
Adenovirus type 5 transformed mouse cells elicit a potent cytotoxic T lymphocyte (CTL) response. Researchers identified a new Ad5E1B epitope, demonstrating that targeting multiple tumor epitopes can enhance cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Adenovirus type 5 (Ad5) transformed mouse embryo cells (MECs) are highly immunogenic.
- Cytotoxic T lymphocytes (CTLs) cloned from Ad5E1 MEC-immunized mice eradicated tumors.
- These CTLs targeted an Ad5E1A-encoded epitope presented by H-2Db.
Purpose of the Study:
- To investigate CTL responses against Ad5E1 MECs with mutated Ad5E1A epitopes.
- To identify novel CTL epitopes on Ad5E1-transformed tumor cells.
- To explore the potential of targeting multiple tumor epitopes for cancer immunotherapy.
Main Methods:
- Generation of Ad5E1 MECs with mutated Ad5E1A-encoded epitopes.
- Induction of CTL responses in immunocompetent mice.
- Cloning and characterization of CTLs against mutant Ad5E1 MECs.
- Assessment of tumor eradication in nude mice.
Main Results:
- Mutant Ad5E1 MECs induced a strong CTL response.
- CTL clones recognized an Ad5E1B-encoded epitope (VNIRNCCYI) presented by H-2Db.
- Ad5E1-transformed tumor cells express at least two distinct CTL epitopes.
- Both Ad5E1A- and Ad5E1B-specific CTLs eradicated established Ad5E1-induced tumors in vivo.
- Activated ras oncogene diminished lysis by Ad5E1B-specific CTLs.
Conclusions:
- Ad5E1-transformed tumor cells express multiple CTL epitopes, including Ad5E1A and Ad5E1B.
- Targeting distinct CTL epitopes on tumors holds promise for effective cancer immunotherapy.
- The ras oncogene may influence the immunogenicity of Ad5E1B-specific CTL targets.
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