Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells

Background
Chimeric antigen receptor (CAR)-T cells face many obstacles in solid tumor therapy, including heterogeneous antigen expression and inefficient T cell persistence. Guanylyl cyclase C (GUCY2C) has been identified as a suitable tumor antigen f…

Neurofilament light chain levels as an early predictive biomarker of neurotoxicity after CAR T-cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant cause of morbidity associated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Early prediction of patients who will develop ICANS would be crucial …

BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma

Background
Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.

Me…

Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy

Background
Pediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due…

Regression of renal cell carcinoma by T cell receptor-engineered T cells targeting a human endogenous retrovirus

Background
We discovered a novel human endogenous retrovirus (CT-RCC HERV-E) that was selectively expressed in most clear cell renal cell carcinomas (ccRCC) and served as a source of antigens for T cell-mediated killing. Here, we described the cloning…

Identification of Siglec-10 as a new dendritic cell checkpoint for cervical cancer immunotherapy

Background
The occurrence of chronic inflammation resulting from infection with human papillomaviruses is an important factor in the development of cervical cancer (CC); thus, deciphering the crosstalk between the tumor microenvironment and innate imm…

NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors

Background
Antitumor effect of chimeric antigen receptor (CAR)-T cells against solid tumors is limited due to various factors, such as low infiltration rate, poor expansion capacity, and exhaustion of T cells within the tumor. NR4A transcription facto…

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy

Background
Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and me…

Preclinical activity of allogeneic SLAMF7-specific CAR T-cells (UCARTCS1) in multiple myeloma

Background
Autologous BCMA-specific CAR T-cell therapies have substantial activity in multiple myeloma (MM). However, due to logistical limitations and BCMAlow relapses, there is a need for alternatives. UCARTCS1 cells are ‘off-the-shelf’ …

Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells

Background
Natural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate end…

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