An effective immunization and cancer treatment with activated dendritic cells transduced with full-length wild-type

E Y Nikitina1, S Chada, C Muro-Cacho

  • 1H Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA.

Gene Therapy
|April 9, 2002
PubMed

Insights

Cancer immunotherapy using p53-based vaccines shows promise. Activated dendritic cells (DCs) engineered to express p53 successfully generated anti-tumor immunity in mice, breaking self-tolerance without causing autoimmune reactions.

Area of Science:

  • Immunology
  • Cancer Research
  • Gene Therapy

Background:

  • P53 protein accumulates in tumors, making it a target for cancer immunotherapy.
  • Generating an immune response against self-proteins like p53 in vivo remains a challenge.
  • Dendritic cells (DCs) are crucial for initiating immune responses.

Purpose of the Study:

  • To investigate the potential of p53-based cancer immunotherapy using modified dendritic cells.
  • To determine if an immune response against self-protein p53 can be generated in vivo.
  • To evaluate the efficacy of activated Ad-p53-transduced DCs in breaking immune tolerance.

Main Methods:

  • Mouse dendritic cells (DCs) were transduced with an adenoviral construct carrying p53 (Ad-p53).
  • Immunizations were performed using Ad-p53-transduced DCs, with and without CD40 activation.
  • Therapeutic efficacy was assessed in MethA sarcoma tumor-bearing mice.
  • Immune response specificity was confirmed via CTL assays and pathological evaluation.

Main Results:

  • Repeated immunizations with Ad-p53 DCs protected 60% of mice against tumor challenge.
  • CD40 activation of DCs significantly enhanced protection, leading to 100% survival.
  • Treatment with activated Ad-p53 DCs resulted in complete tumor rejection in 4 out of 6 mice.
  • No signs of autoimmune reactions were observed in treated mice.

Conclusions:

  • Activated Ad-p53-transduced DCs can effectively break immune tolerance to self-protein p53.
  • This approach demonstrates potential for developing novel cancer immunotherapies.
  • The combination of p53 expression and DC activation enhances anti-tumor immune responses.

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