Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors

Mol Cancer. 2024 May 10;23(1):98. doi: 10.1186/s12943-024-02007-w.

Abstract

The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs in this domain. Their investigation reveals the pronounced augmentation of anti-tumor activity in CAR T cells through the introduction of a T cell neoplasm fusion gene, CARD11-PIK3R3. The incorporation of this gene into engineered T cell therapy holds promise as a formidable tool in the arsenal of cancer immunotherapy. The innovative strategy outlined not only mitigates the requirement for high doses of CAR T cells but also enhances tumor control while exhibiting encouraging safety profiles. The exploration of the CARD11-PIK3R3 fusion gene represents an advancement in our approach to bolstering the anti-tumor efficacy of immunotherapeutic interventions. Nonetheless, the imperative for further inquiry to ascertain its transfection efficiency and long-term safety cannot be overstated. Nevertheless, this seminal investigation offers a beacon of hope in surmounting the formidable treatment impediments posed by solid tumors, paving the way for a transformative era in cancer therapeutics.

Keywords: Adoptive cell transfer therapy; CAR T cells; CARD11-PIK3R3; Cancer immunotherapy; Solid tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Letter

MeSH terms

  • Animals
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / immunology
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment / immunology

Substances

  • Receptors, Chimeric Antigen