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…

Novel tetrameric bispecific KK-LC-1xCD16A-armed memory-like NK cells enhance antitumor efficacy in gastric cancer

Background
Cytokine-induced memory-like natural killer (CIML NK) cells demonstrate potent antitumor efficacy against hematological malignancies. Nevertheless, the therapeutic potential of adoptive NK cell transfer remains constrained in solid tumors d…

Intraperitoneal CAR T-cell therapy for peritoneal carcinomatosis from gastroesophageal cancer: preclinical investigations to a phase I clinical trial (NCT06623396)

Peritoneal carcinomatosis is a frequent metastatic condition in gastroesophageal cancer and is associated with poor prognosis and limited therapeutic options. Here, we establish clinically relevant mouse models of peritoneal carcinomatosis to evaluate…

Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL

Background
Despite the curative potential for chimeric antigen receptor (CAR) T-cells in B-cell acute lymphoblastic leukemia (B-ALL), efficacy can be limited by life-threatening adverse events such as severe infections. As immune effector cell-associa…

Genome editing or small molecule inhibition of KMT5A in CAR-T cells enhances antitumor immunity

Background
Adoptive T-cell therapy has emerged as a promising therapeutic strategy for cancer treatment. However, clinical challenges persist, including the limited ability of CD8+T cells to infiltrate solid tumors and efficiently eliminate tumor cell…

Tandem CAR-T cells targeting mesothelin and MUC16 overcome tumor heterogeneity by targeting one antigen at a time

Background
Tumor heterogeneity and antigen escape are mechanisms of resistance to chimeric antigen receptor (CAR)-T cell therapy, especially in solid tumors. Targeting multiple antigens with a unique CAR construct could be a strategy for a better tumo…

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