CAR-T cell therapy targeting MUC17 in gastric tumors

Background
Chimeric antigen receptor (CAR)-T cell therapy has achieved significant success in hematologic malignancies; however, its efficacy in solid tumors remains limited. A major limitation is the difficulty in identifying suitable target antigens…

Oncolytic virus-induced IL-1{beta}+ monocyte-IL-6+ CAF axis suppresses dendritic cell-mediated antitumor immunity in pancreatic cancer

Background
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a profoundly immunosuppressive tumor microenvironment, which features a dense desmoplastic stroma enriched with cancer-associated fibroblasts (CAFs) that collectively impede the ef…

Novel antibodies for identification, selection, and manipulation of T cells expressing Whitlow linker-containing CARs

Background
The translational study of chimeric antigen receptor (CAR) T-cell function, persistence, immunophenotype, and spatial localization after infusion is crucial for understanding factors that influence clinical outcomes. However, research has b…

Prognosis and treatment response stratification according to loss of proofreading (LOP) POLE variants

Background
Only a subset of polymerase epsilon (POLE) mutations is associated with hypermutant phenotype; we hypothesized that only loss-of-proofreading (LOP) POLE mutations are associated with favorable immunotherapy response.

Methods
This retrospec…

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…

Endothelial cells as targets of immune checkpoint blockade

The tumor vasculature acts as the gatekeeper to the tumor microenvironment, thus regulating the ability of immune cells to roll, anchor, and cross the endothelium from blood to tissue. While the role of endothelial cells (EC) in T Cell migration and e…

A bispecific antibody targeting PD-L1/TNFR2 increases tumor targeting and enhances antitumor efficacy in colorectal cancer

Background
Immune checkpoint inhibitors (ICIs) have shown limited efficacy in colorectal cancer (CRC), largely due to immunosuppressive tumor microenvironment (TME) including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Add…

TAMs-mediated resistance to oncolytic virus M1 in solid tumors

Background
Oncolytic virus M1 (OVM), a naturally occurring alphavirus, has demonstrated potent antitumor activity in various solid tumor models by inducing immunogenic cell death and activating CD8+ T cells. However, its in vivo efficacy varies widely…

Identification of conserved immune-related adverse event risk factors and clinical outcomes in a pan-immunotherapy data mart

Background
Cancer immunotherapy (CIT) often triggers immune-related adverse events (irAEs). Analysis of irAEs in large checkpoint inhibitor (CPI) trials has enhanced their management and demonstrated their prognostic value for treatment outcome. Howev…

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…

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