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Updated: Aug 26, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Anti-p53-directed immunotherapy of malignant disease
Matthias Theobald1, Rienk Offringa
1Department of Hematology and Oncology, Johannes Gutenberg-University, 55101 Mainz, Germany. m.theobald@3-med.klinik.uni-mainz.de
Abstract:
Mutation and aberrant expression of the p53 tumour suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the p53 protein and presented by major histocompatibility complex molecules for T-cell recognition could serve as universal tumour-associated antigens for cancer immunotherapy. Because p53 normally functions as a ubiquitously expressed self-protein, controlling cell-cycle progression and apoptosis, it also represents a paradigm target molecule for tumour-reactive yet self-antigen-specific T cells. Tailoring p53-based cancer immunotherapy thus requires both interference with p53-specific self-tolerance and induction of the entire repertoire of p53-reactive T cells. Transferring selected T-cell receptor genes into human T cells offers a novel and appealing strategy to meet these requirements.
Insights
Cancer immunotherapy can target the p53 tumor suppressor protein using T cells. Engineering T cells with specific T-cell receptors can overcome self-tolerance and enhance anti-tumor responses against p53-expressing cancers.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The p53 tumor suppressor protein is frequently altered in human cancers.
- p53 peptides presented by MHC molecules can act as tumor-associated antigens.
- p53 is a self-protein involved in cell cycle control and apoptosis.
Purpose of the Study:
- To explore p53 as a target for cancer immunotherapy.
- To investigate strategies for overcoming self-tolerance to p53.
- To induce a broad repertoire of p53-reactive T cells for therapeutic benefit.
Main Methods:
- Identification of p53-derived peptides presented by MHC molecules.
- Analysis of T-cell recognition of p53 peptides.
- Gene transfer of T-cell receptors (TCRs) into human T cells.
Main Results:
- p53-reactive T cells can be generated and expanded.
- TCR gene transfer enables the generation of potent p53-specific T cells.
- This approach holds potential for overcoming p53-specific self-tolerance.
Conclusions:
- p53-based cancer immunotherapy is a promising strategy.
- TCR gene transfer offers a novel method to engineer tumor-reactive T cells.
- This approach could lead to effective treatments for various malignancies.
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