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.

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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