Background T cell receptor (TCR)-T based therapies, such as MAGE-A4 TCR-T cells, have shown compelling data demonstrating effective infiltration into and targeting of solid tumours with clinical responses across various solid cancers.1 However, heterogeneity and down-regulation of target expression limit the durability and curative potential of these types of treatments. On the other hand, owing… Continue reading 349 A novel ‘off the shelf TCR-NK cell therapy platform for the treatment of solid tumours: development of optimised MAGE-A4 targeting TCR-NK cells for advancement into the clinic
Tag: Biochemical Pharmacology
331 Functional enhancement of T cells by the co-expression of IL-7 and dominant-negative TGF{beta}RII
AI SummaryCo-expression of IL-7 and dnTGFβRII on TILs and CAR-T cells enhances their antitumor activity and resistance to immunosuppression. The combination of IL-7 signaling enhancement and TGF-β inhibition synergistically improves T cells’ efficacy against tumors.Background The effect of transforming growth factor β (TGF-β) is cell type- and context-dependent. In the tumor microenvironment, TGF-β restricts T… Continue reading 331 Functional enhancement of T cells by the co-expression of IL-7 and dominant-negative TGF{beta}RII
344 Human macrophages lacking NF-{kappa}B p50 display increased proinflammatory cytokine expression
AI SummaryResearchers have developed a method to generate human immature myeloid cells lacking the NF-B p50 protein (p50-IMC) for potential clinical applications. These cells showed increased expression of proinflammatory genes and decreased expression of suppressive genes. The findings suggest that p50-IMC may be a therapeutic approach for slowing the growth of certain types of cancer.Background… Continue reading 344 Human macrophages lacking NF-{kappa}B p50 display increased proinflammatory cytokine expression
338 Comparison of lymphodepleting chemotherapy regimens as preconditioning for T-cell therapies
AI SummaryLymphodepletion regimens were compared using a mathematical model to determine the most effective regimen for promoting expansion and function of engineered T-cells. The results showed that the most effective regimen was fludarabine 30 mg/m2/day for 4 days and cyclophosphamide 1800 mg/m2/day for 2 days. However, there was not much difference between the tested regimens… Continue reading 338 Comparison of lymphodepleting chemotherapy regimens as preconditioning for T-cell therapies
303 PiggyBac transposon-mediated HER2-CAR-T cells exert anti-tumor efficacy against cholangiocarcinoma
AI SummaryA study evaluated the anti-tumor efficacy of a HER2-CAR-T cell therapy (BP2301) in a cholangiocarcinoma xenograft model. The therapy demonstrated killing activity against tumor cells, eradicated tumors in some mice, and showed long-term persistence. The study supports the potential use of BP2301 as a treatment option for cholangiocarcinoma patients with HER2 expression.Background Cholangiocarcinoma (CCA)… Continue reading 303 PiggyBac transposon-mediated HER2-CAR-T cells exert anti-tumor efficacy against cholangiocarcinoma
294 Comparison of preclinical efficacy between CD19 CAR-T and CD3xCD19 bispecific antibody (blinatumomab)
AI SummaryBispecific antibodies and CAR-T are both effective cancer therapies, but limited research has compared the two. This study compared the efficacy of CD19 CAR-T and CD3xCD19 bispecific antibodies in vitro and in vivo. The results showed similar tumor suppression in vitro, but CAR-T had a better in vivo response and maintained remission better due… Continue reading 294 Comparison of preclinical efficacy between CD19 CAR-T and CD3xCD19 bispecific antibody (blinatumomab)
293 Development of a MUC16-specific CAR-T cell exhibiting potent antitumor activity for the treatment of patients with recurrent ovarian cancer
Background Despite significant improvements in surgical and medical treatments, ovarian cancer remains the most lethal gynecologic malignancy, with a 2-to 3-year recurrence rate, highlighting an unmet need for effective therapeutic options for patients.1 Mucin 16 (MUC16) is a type I integral membrane glycoprotein that is overexpressed in more than 80% of ovarian cancers.2 Proteolytic cleavage… Continue reading 293 Development of a MUC16-specific CAR-T cell exhibiting potent antitumor activity for the treatment of patients with recurrent ovarian cancer
231 Differential effects of target ligands and receptor architecture upon NKG2D CAR T cell activation
AI SummaryThe NKG2D receptor binds to stress-induced ligands, which are often expressed in tumors. The binding affinity of NKG2D to its ligands and the effect of different ligands on immune response are not completely understood. Researchers created CAR T-cells with the NKG2D receptor and found that different ligands led to varying levels of cytokine secretion… Continue reading 231 Differential effects of target ligands and receptor architecture upon NKG2D CAR T cell activation
237 Epitope engineered hematopoietic stem cells to enable multi-specificity CAR-T cells for acute myeloid leukemia
Background Acute myeloid leukemia (AML) is associated with an unfavorable outcome for >50% of patients. Whereas novel immunotherapies, such as CD19-CAR-T, demonstrated striking efficacy when targeting dispensable antigens (Ag), the same approach cannot be exploited for AML, due to lack of actionable leukemia-restricted Ags. AML targets are shared with progenitors (HSPCs) or mature myeloid cells,… Continue reading 237 Epitope engineered hematopoietic stem cells to enable multi-specificity CAR-T cells for acute myeloid leukemia
259 Discovery of synthetic signaling pathway receptors that increase the potency of CAR-T cells through optimized STAT activity
AI SummarySynthetic receptors called Synthetic Pathway Activators (SPAs) have been developed to enhance the function of chimeric antigen receptor (CAR) T cells in solid tumors. These SPAs engage constitutive STAT signaling, leading to improved antitumor activity in preclinical assays. The SPA-expressing T cells have increased expansion and retention of effector function, resulting in complete clearance… Continue reading 259 Discovery of synthetic signaling pathway receptors that increase the potency of CAR-T cells through optimized STAT activity