JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian cancer models

Background
Boosting the performance of chimeric antigen receptor T (CAR-T) cell therapy in solid tumors may provide a substantial advantage for patients with cancer. Recognizing the vital role of the nuclear factor of activated T cells (NFAT) in T cel…

Increased NFAT activity with dual CAR stimulation in CD19xCD22 CAR T-cells is associated with decreased exhaustion and improved survival

Background
Chimeric antigen receptor (CAR) T-cell therapy is effective in treating B-cell malignancies, however relapse due to lack of CAR persistence and antigen-modulated escape remains common. Multiple strategies to simultaneously target CD19 and C…

Targeting the extracellular matrix with Tenascin-C-specific CAR T cells extends survival in preclinical models of glioblastoma

Background
Glioblastoma (GBM) is an aggressive brain tumor associated with poor outcome and limited treatment options. Chimeric antigen receptor (CAR) T cells targeting cell surface antigens were shown to induce tumor regression in patients with GBM, …

Acquisition of an immunosuppressive microenvironment after anti-CD19 CAR T-cell therapy is associated with T-cell dysfunction and resistance

Background
Chimeric antigen receptor (CAR) T cells targeting CD19 induce durable responses in B-cell acute lymphoblastic leukemia (B-ALL). However, the contribution of the tumor microenvironment to the therapeutic response after CAR T-cell treatment r…

Acquisition of an immunosuppressive microenvironment after anti-CD19 CAR T-cell therapy is associated with T-cell dysfunction and resistance

Background
Chimeric antigen receptor (CAR) T cells targeting CD19 induce durable responses in B-cell acute lymphoblastic leukemia (B-ALL). However, the contribution of the tumor microenvironment to the therapeutic response after CAR T-cell treatment r…

Macrophages expressing chimeric cytokine receptors have an inflammatory phenotype and antitumoral activity upon IL-10 or TGF{beta} stimulation

Background
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks hormone receptors and human epidermal growth factor receptor 2 (HER2) amplification, making it unresponsive to standard hormone or HER2-targeted…

Envirotune-CAR-T: a hypoxia-responsive and glutamine-enhanced CAR-T cell therapy for overcoming tumor microenvironment-mediated suppression

Background
Chimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable success in hematologic malignancies; however, its efficacy in solid tumors remains limited. A major barrier is the immunosuppressive tumor microenvironment (TME), wh…

Claudin 6 is a suitable target for CAR T-cell therapy in atypical teratoid/rhabdoid brain tumors and other pediatric solid tumors

Background
Solid tumors comprise approximately 60% of all pediatric cancers. Relapsed or refractory tumors of the central nervous system (CNS), such as atypical teratoid/rhabdoid tumors (AT/RTs), are the leading cause of death in children with cancer….

Germline determinants of toxicity and efficacy in patients with large B-cell lymphoma treated with CAR T-cell therapy

Background
Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline deter…

Mechanistic data-informed multiscale quantitative systems pharmacology modeling framework enables the clinical translation and efficacy assessment of CAR-T therapy in solid tumors

Background
Chimeric antigen receptor (CAR)-T cell therapy represents an innovative and potentially revolutionary modality in cancer treatment. Despite their great success in treating blood cancers, CAR-T therapies exhibit significantly lower effective…

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