CAR-T Cell Therapy in Solid Tumors: A Systematic Review of Clinical Evidence, Translational Barriers, and Emerging Therapeutic Strategies

Kyprianos Kottis

doi:10.36948/ijfmr.2026.v08i03.78493

CAR-T Cell Therapy in Solid Tumors: A Systematic Review of Clinical Evidence, Translational Barriers, and Emerging Therapeutic Strategies

Author(s)	Kyprianos Kottis
Country	Germany
Abstract	Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of selected hematologic malignancies, but its translation to solid tumors remains constrained by antigen heterogeneity, impaired trafficking, stromal exclusion, tumor microenvironment-mediated exhaustion, and on-target off-tumor toxicity. This systematic literature review provides a comprehensive overview of clinical and translational data on CAR-T cell therapy for solid malignancies, and a focused PubMed-based search update through 5 May 2026. Qualified studies included human clinical trials with autologous or allogeneic CAR-T treatments in solid cancers reporting efficacy, safety, pharmacodynamic, or biomarker results. Narrative synthesis of evidence was performed due to significant differences in tumor type, antigen target, CAR construct, delivery method, lymphodepletion method, and outcome reporting. The new evidence base shows that durable objective responses are rare in conventional single-agent intravenous CAR-T therapy, but promising signals have arisen in certain contexts. Randomized Phase II data provide the strongest evidence for the use of CLDN18.2-directed satricabtagene autoleucel in advanced gastric/gastroesophageal junction (GEJ) cancer, demonstrating improvements in progression-free survival and overall survival compared with physician's choice therapy. There has also been significant progress in delivering CAR-Ts to the CNS at the local level, and treatment with IL13Rα2-, EGFR/IL13Rα2-, or B7-H3-targeting CAR-T is feasible, tolerable, and radiographically or biologically active in recurrent high-grade glioma, glioblastoma, and diffuse intrinsic pontine glioma, respectively. There are also early-phase data that further validate engineered therapies such as hypoxia-responsive, CEA-targeted CAR-T cells. Overall, the results indicate that the key elements of successful solid-tumor CAR-T therapy will likely be multimodal approaches that involve antigen targeting, regional delivery, multi-antigen and/or logic-gated targeting, modulation of the tumor microenvironment, and standardized reporting of response and toxicity.
Keywords	CAR-T cell therapy; solid tumors; chimeric antigen receptor T cells; CLDN18.2; glioblastoma; tumor microenvironment; locoregional delivery; systematic review
Field	Biology
Published In	Volume 8, Issue 3, May-June 2026
Published On	2026-05-15
DOI	https://doi.org/10.36948/ijfmr.2026.v08i03.78493

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CAR-T Cell Therapy in Solid Tumors: A Systematic Review of Clinical Evidence, Translational Barriers, and Emerging Therapeutic Strategies

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