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Related Experiment Videos

Targeting p53 for adoptive T-cell immunotherapy

T M McCarty1, X Liu, J Y Sun

  • 1Department of Surgery, City of Hope National Medical Center, Duarte, California 91010, USA.

Cancer Research
|July 4, 1998
PubMed
Summary
This summary is machine-generated.

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High-affinity T cells targeting the p53 tumor suppressor protein effectively suppressed tumor growth in mice. This study demonstrates the potential of p53-specific T cell therapy for cancer treatment.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Therapy

Background:

  • p53 gene mutations are prevalent in human cancers, leading to altered p53 protein accumulation.
  • Endogenous human T cell responses to p53 are typically weak.
  • Previous research generated high-affinity p53-specific T cells (CTLs) in HLA A2.1 transgenic mice.

Purpose of the Study:

  • To investigate the efficacy of HLA A2.1-restricted, p53-specific CTLs in suppressing p53-overexpressing human tumors.
  • To evaluate the therapeutic potential of adoptive T cell transfer in a mouse model.

Main Methods:

  • Generated and characterized murine p53(149-157)-specific CTLs restricted by HLA A2.1.
  • Assessed CTL-mediated lysis of p53-overexpressing Panc-1 cancer cells and control cells in vitro.

Related Experiment Videos

  • Administered p53-specific CTLs to SCID mice bearing established human tumor xenografts.

    • Main Results:

    • In vitro, p53(149-157)-specific CTLs selectively lysed p53-overexpressing Panc-1 cells but not control cells.
    • In vivo, adoptive transfer of p53-specific CTLs significantly reduced tumor growth and prolonged survival in SCID mice.
    • Immunohistochemistry confirmed infiltration of CD8+ CTLs into regressing Panc-1 tumors post-treatment.

    Conclusions:

    • HLA A2.1-restricted, p53(149-157)-specific murine CTLs effectively suppress established p53-overexpressing tumor growth.
    • Adoptive transfer of these CTLs prolongs host survival in SCID mice.
    • These findings support the therapeutic potential of p53-specific CTLs for cancer treatment.