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

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.

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Cancer Vaccines01:30

Cancer Vaccines

Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...