The intersection of CAR-T immunotherapy with emerging technologies

Coşar B., Kılıç P., İşeri Ö. D.

Cytokine and Growth Factor Reviews, vol.86, pp.238-259, 2025 (SCI-Expanded, Scopus)

  • Publication Type: Article / Review
  • Volume: 86
  • Publication Date: 2025
  • Doi Number: 10.1016/j.cytogfr.2025.11.001
  • Journal Name: Cytokine and Growth Factor Reviews
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.238-259
  • Keywords: Chimeric antigen receptor (CAR) T-cell (CAR-T), Cytokine signaling, Growth factor pathways, Metabolic reprogramming, Next-generation engineered T-cells, Tumor microenvironment (TME)
  • Ankara University Affiliated: Yes

Abstract

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy is a transformative modality in cancer immunotherapy that employs genetically engineered T-cells to eliminate malignant cells selectively. Its efficacy and limitations are governed by cytokine- and growth factor–mediated signaling networks that shape T-cell activation, proliferation, differentiation, and persistence. This review traces the molecular evolution of CAR-T architecture across generations, highlighting how synthetic modulation of cytokine and co-stimulatory pathways enhances potency while reducing exhaustion and toxicity. We discuss strategies that incorporate cytokine engineering, metabolic reprogramming, and logic-gated activation to counteract the immunosuppressive tumor microenvironment. Recent technological advances—such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9)-based cytokine pathway editing, induced pluripotent stem cell (iPSC)–derived “off-the-shelf” CAR-T platforms, and extracellular vesicle (EV)–mediated cytokine delivery—are reshaping adoptive immunotherapy. Framing CAR-T development through the lens of cytokine and growth factor biology, we outline how integrating these pathways enables safer, more durable, and scalable next-generation therapies for hematologic and solid tumors.