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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Preventive vaccination with telomerase controls tumor growth in genetically engineered and carcinogen-induced mouse

Carmela Mennuni1, Stefano Ugel, Federica Mori

  • 1Istituto di Ricerca di Biologia Molecolare, Pomezia, Italy.

Cancer Research
|December 3, 2008
PubMed

Insights

Cancer vaccination targeting telomerase reverse transcriptase (TERT) shows promise. DNA vaccination with murine TERT (mTERT) effectively delayed tumor growth in mouse models, inducing antigen-specific T cell responses with no observed adverse effects.

Area of Science:

  • Immunology
  • Oncology
  • Vaccinology

Background:

  • Telomerase reverse transcriptase (TERT) is reactivated in many human cancers, making it a potential target for cancer vaccines.
  • Genetic vaccination using murine TERT (mTERT) can overcome immune tolerance and induce TERT-specific T cell responses.

Purpose of the Study:

  • To investigate the antitumor efficacy and safety of TERT-based vaccination in preclinical cancer models.
  • To evaluate the induction of immune responses following mTERT vaccination.

Main Methods:

  • Utilized TRAMP transgenic mice for prostate cancer and a carcinogen-induced model for colon cancer.
  • Administered repeated immunizations with mTERT-encoding DNA.
  • Assessed tumor progression, immunohistochemistry for TERT expression, and intratumoral T cell infiltrates.
  • Conducted postnecropsy analysis for safety assessment.

Main Results:

  • Repeated mTERT DNA vaccination significantly delayed tumor formation and progression in both prostate and colon cancer models.
  • TERT-specific CD4+ and CD8+ T cells were induced, and telomerase-specific T cells were found in tumor infiltrates of vaccinated mice.
  • Vaccination demonstrated a good safety profile with no significant adverse effects or organ damage.

Conclusions:

  • TERT vaccination elicits antigen-specific immunosurveillance and demonstrates significant antitumor efficacy in relevant preclinical models.
  • TERT represents a promising candidate antigen for the development of preventive cancer vaccines.

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