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…

Comparative efficacy and safety of PSCA CAR-engineered V{delta}1 {gamma}{delta} T cells for immunotherapy of pancreatic cancer

Background
T cells possess unique immunological features including tissue tropism, major histocompatibility complex-independent antigen recognition, and hybrid T/natural killer cell properties that make them promising candidates for cancer immunother…

CD33KO-CD33-mesothelin Loop CAR design avoids fratricide and improves efficacy of iNK cells against acute myeloid leukemia

Background
Patients with acute myeloid leukemia (AML) are often older, which brings challenges of endurance and persistent efficacy of autologous chimeric antigen receptor (CAR)-T cell therapies. Allogenic CAR-natural killer (NK) cell therapies may of…

Preclinical evaluation of antitumor activity and toxicity of TROP2-specific CAR-T cells for treatment of triple-negative breast cancer

Background
Triple-negative breast cancer (TNBC) represents a subtype of breast cancer with poorest prognosis due to limited effective targeted therapies. Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable efficacy in treating hemato…

Efficacy and safety of one-time autologous tumor-infiltrating lymphocyte cell therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

Background
Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a high recurrence rate after first-line immunotherapy or chemoimmunotherapy. The presence of a high density of tumor-infiltrating lymphocytes (TILs) in HNSCC tumo…

An affinity-modulated T cell engager targeting Claudin 18.2 shows potent anti-tumor activity with limited cytokine release

Background
AZD5863 is a bispecific T cell engager (TCE) with high affinity to CLDN18.2 and low affinity to cluster of differentiation 3 (CD3), designed to decrease its peripheral cytokine release potential, improve the therapeutic index, and maintain …

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