Safety enhancements - such as reversible CAR inhibition using Dasatinib and GM-CSF neutralization - are also being explored to mitigate toxicity...Ongoing research continues to identify new strategies to further refine these therapies, including the exploration of combination treatments with checkpoint inhibitors and novel immunomodulatory agents. As our understanding of the tumor microenvironment deepens, the potential for personalized approaches to CAR T-cell therapy may unlock even greater therapeutic benefits for patients.

Additionally, combining CAR-T therapy with surgery may reduce tumor recurrence and positively influence reconstructive outcomes. Overall, this review underscores CAR-T cell therapy as a potential adjunctive treatment in oncologic surgery, emphasizing the importance of interdisciplinary approaches to improve patient outcomes in solid tumor management.

EGFR TKIs upregulate TnMUC1 by reducing MUC1 glycosylation, thereby improving TnMUC1 CAR-T cell recognition and cytotoxicity. Specifically, EGFR TKIs modulate TnMUC1-related glycosyltransferases, with core1-beta1,3-galactosyltransferase 1 (C1GALT1) identified as a key enzyme downregulated by EGFR TKIs, suggesting C1GALT1 as a potential therapeutic target.

Additionally, this review also evaluates combination therapies of immune checkpoint inhibitors and recently published clinical trials on lung cancer with CAR T cells. We offer insights into the way to optimize CAR T cell therapy for lung cancer by analyzing antigen selection, immune evasion, and the strategies to enhance T cell persistence and tumor infiltration.

P=N/A, N=20, Recruiting, Obstetrics & Gynecology Hospital of Fudan University

P1, N=180, Active, not recruiting, Poseida Therapeutics, Inc. | Recruiting --> Active, not recruiting

P1, N=180, Recruiting, Poseida Therapeutics, Inc. | N=100 --> 180

Intratumoral treatment effectively reduced distant tumors, suggesting retention of antigen-recognition benefits at metastatic sites. Overall, we provide preclinical evidence of armored non-alloreactive MUC1 CAR T cells greatly reducing high TNBC tumor burden in a TGFB1- and PD-L1-rich TME both at local and distant sites while preserving safety.

Key genes identified in the oncogenic pathways of ovarian cancers included MUC1, CXCR4, EPCAM, RACGAP1, UBE2C, PRAME, SORT1, JUP, and CLDN3, suggesting them as recommended antigens for CAR-T-cell therapy for ovarian cancers. This study sheds light on potential targets for immunotherapy in ovarian cancers.

P1, N=30, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Trial completion date: Aug 2026 --> Aug 2036 | Trial primary completion date: Aug 2024 --> Aug 2026

A vascularized microfluidic device was developed that allowed CAR T cells to flow through the vessels and penetrate the gels in a more physiological way, killing malignant cells in a TNFα-dependent manner. Complex 3D human cell models may provide an efficient way of screening multiple cytotoxic human immune cell constructs while also enabling evaluation of mechanisms of resistance involving cell-cell and cell-matrix interactions, thus accelerating preclinical research on cytotoxic immune cell therapies in solid tumors.

We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.