Eradication of adenovirus E1-induced tumors by E1A-specific cytotoxic T lymphocytes

W M Kast1, R Offringa, P J Peters

  • 1The Netherlands Cancer Institute, Amsterdam.

Cell
|November 17, 1989
PubMed

Insights

Cytotoxic T lymphocytes (CTLs) targeting adenovirus E1A oncogenes effectively eradicate tumors in mice. This immunotherapy approach establishes long-lasting anti-tumor memory, demonstrating its therapeutic potential.

Area of Science:

  • Immunology
  • Oncology
  • Virology

Background:

  • Adenovirus type 5 (Ad5) early region 1 (E1)-transformed cells can induce tumors.
  • Cytotoxic T lymphocytes (CTLs) play a crucial role in anti-viral and anti-tumor immunity.
  • Identifying specific tumor antigens recognized by CTLs is key for developing targeted therapies.

Purpose of the Study:

  • To generate and characterize CTL clones specific for Ad5 E1-transformed cells.
  • To evaluate the therapeutic efficacy of these CTLs in an in vivo tumor model.
  • To investigate the immunological memory generated by this treatment.

Main Methods:

  • Generation of CTL clones from C57BL/6 mice immunized against Ad5 E1-transformed cells.
  • Identification of the target peptide encoded by Ad5 E1A.
  • In vivo therapy using CTLs and IL-2 in B6 nude mice bearing Ad5 E1-induced tumors.

Main Results:

  • Defined Ad5 E1A peptide recognized by H-2Db-restricted CTLs.
  • Intravenous administration of CTLs combined with IL-2 led to significant tumor regression (up to 10 cm3).
  • Long-term anti-tumor immunological memory was observed in treated mice after tumor eradication.

Conclusions:

  • CTLs targeting a viral oncogene product (Ad5 E1A) are effective in eradicating established tumors.
  • This CTL-based immunotherapy demonstrates high specificity and induces durable anti-tumor memory.
  • Targeting viral oncogenes with CTLs represents a promising strategy for cancer immunotherapy.

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