biostudies-literatureSupper VMNational Cancer Institute (NCI)American Cancer SocietyNational Cancer InstituteNCI NIH HHSAmerican Cancer Society (ACS)1132-1144https://www.ebi.ac.uk/biostudies/studies/S-EPMC12777652biostudies-literatureUnknown13(8)Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment strategy for B-cell malignancies; however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature; however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic benefit. Increasing evidence suggests a role for VEGF in the immunosuppressive tumor microenvironment, including through direct induction of T cell-effector dysfunction. In this study, we show that CAR T cells from patients treated with FDA-approved CAR T-cell products express members of the VEGF signaling pathway, and this expression is correlated with patient nonresponse. To overcome putative VEGF-induced CAR T-cell dysfunction and deliver local VEGF bloCancer immunology researchSecretion of a VEGF-Blocking scFv Enhances CAR T-cell Potency.PMC12777652K08 CA289948-02K08 CA289948R01 CA238268YACS-24-1334735-01-YACSLeick MBBratt ABirocchi FChoi BDKorell FPhilips MPark STakei HParker AArmstrong AMartin GKienka TDonner HBouffard ASalas-Benito DGoncalves SKann MCMaus MVSupper VMEscobar GBailey SRHaradhvala NJDarnell EPfalseSecretion of a VEGF-Blocking scFv Enhances CAR T-cell Potency.Chimeric antigen receptor (CAR) T-cell therapy is an effective treatment strategy for B-cell malignancies; however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature; however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic benefit. Increasing evidence suggests a role for VEGF in the immunosuppressive tumor microenvironment, including through direct induction of T cell-effector dysfunction. In this study, we show that CAR T cells from patients treated with FDA-approved CAR T-cell products express members of the VEGF signaling pathway, and this expression is correlated with patient nonresponse. To overcome putative VEGF-induced CAR T-cell dysfunction and deliver local VEGF blo2025-01-01T00:00:00Z2025 Aug2026-06-06T12:37:33.802Z2026-05-30T03:11:26.627ZS-EPMC127776524045506410.1158/2326-6066.cir-24-087610.1158/2326-6066.CIR-24-0876