• Gene Therapy-Driven CAR-T Cell Therapy: A New Horizon for Immune System Activation in Cancer Treatment
  • Arezoo Hassani,1,*
    1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.


  • Introduction: Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking immunotherapeutic strategy, leveraging gene editing to empower a patient's own T cells to detect and destroy cancer cells. Since its initial FDA approval, CAR-T therapy has shown remarkable success in treating hematological malignancies, particularly in cases resistant to standard treatments. The goal of this review is to explore how gene therapy-based CAR-T technology activates the immune system, review recent scientific advancements, and highlight the ongoing challenges in extending this approach to solid tumors.
  • Methods: This narrative review was based on a comprehensive literature search conducted across PubMed, Scopus, and Web of Science databases for studies published between 2019 and 2025. Key search terms included “CAR-T cell therapy,” “gene therapy,” “immune activation,” and “cancer immunotherapy.” Articles selected for inclusion were original research papers, clinical trials, and high-impact reviews focusing on immune responses triggered by gene-modified CAR-T cells. Emphasis was placed on up-to-date, peer-reviewed findings.
  • Results: CAR-T therapy involves genetically modifying T cells to express artificial receptors that recognize specific tumor antigens, such as CD19 or BCMA. Upon reinfusion into the patient, these engineered cells target and destroy cancer cells, while also releasing pro-inflammatory cytokines (e.g., IL-2, IFN-γ, TNF-α), initiating a cascade of immune responses that further enhance anti-tumor activity. Recent innovations include “armored” CAR-T cells designed to secrete cytokines or checkpoint inhibitors, enabling them to overcome the immunosuppressive tumor microenvironment. Additionally, the integration of advanced gene-editing tools like CRISPR/Cas9 has allowed the production of universal, allogeneic CAR-T cells by removing native T-cell receptors and HLA molecules to prevent graft-versus-host disease. Despite notable achievements in treating blood cancers, CAR-T therapy faces significant obstacles in solid tumors. These include antigen heterogeneity, physical barriers to T-cell infiltration, and immune evasion mechanisms within the tumor microenvironment. Several strategies are under development to improve CAR-T efficacy in solid tumors, such as the use of dual-targeting CARs and localized cytokine release.
  • Conclusion: Gene therapy-enhanced CAR-T cell therapy is a transformative approach in cancer immunotherapy, capable of activating the immune system with high precision and potency. By combining targeted cytotoxicity with systemic immune activation, it offers new hope for patients with hard-to-treat malignancies. Ongoing research is focused on improving the safety, specificity, and scalability of this therapy, especially for solid tumors. As technologies evolve, the integration of synthetic biology, gene editing, and personalized immunotherapy holds the potential to redefine cancer treatment paradigms.
  • Keywords: CAR-T therapy, gene therapy, immune activation, cancer treatment, CRISPR,