Part of the reason for CAR T cells’ astonishing success in B-cell cancers is that B cells are astonishingly easy to replace. CAR T cells are specific, yes. But they are not specific to tumor cells. They are specific to their target antigens. In the case of Yescarta (axicabtagene ciloleucel, Gilead Sciences Inc.) and Kymriah (tisagenlecleucel, Novartis AG), the first two clinically approved T cells, that target is CD19, which is expressed on B-cell precursors. And when it is successful, the treatment leaves patients without any B cells at all.
Diffuse intrinsic pontine glioma (DIPG) is an almost universally fatal brain pediatric tumor and the only tumor indication where palliative radiotherapy is the current standard of care. Although chimeric antigen receptor (CAR) T-cell therapy may hold promise for treating DIPG, the elevated tumor heterogeneity and the prospect of antigen escape make the identification of additional targets crucial. Therefore, multiple targets need to be validated to facilitate a multipronged approach.
A new study has discovered a promising approach to improve the efficacy of adoptive cell therapies for cancer. The research, published in Molecular Therapy: Nucleic Acids, describes the development of novel Fas-TNFR chimeras acting as decoys for the Fas ligand and preventing it from binding to its natural receptor on the surface of chimeric antigen receptor (CAR) T cells.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the person’s immune system destroys its own pancreatic islet cells that leads to complete loss of insulin production. Allogeneic pancreatic islet cell transplantation has been shown to replenish the vanished β-cell population and provide glycemic control, restoration of hypoglycemia awareness, and protection from severe hypoglycemic events. However, with allogeneic transplantation, there is a need for life-long immunosuppression to protect the islet grafts from allo- and autoimmunity.
Coimmune Inc. has exercised its option to obtain an exclusive license to IL-18 armored chimeric antigen receptor (CAR) technology under a prior agreement with Memorial Sloan Kettering Cancer Center (MSK). The company plans to couple the technology with allogeneic cytokine induced killer (CIK) cells to launch the clinical development of CMN-008 (armored CAR-CIK cells), with CD19 as the initial target in B-cell malignancies.
Over half of the children with high-risk neuroblastoma experience late relapses caused by minimal residual disease. Since chimeric antigen receptor (CAR) T-cell therapy has shown efficacy against minimal residual disease in pediatric patients with hematologic malignancies, several CAR T-cell therapies are being investigated for neuroblastoma.
Mesothelin (MSLN) glycoprotein is overexpressed in many solid tumors and is considered a relevant target for antigen-specific therapies. In fact, chimeric antigen receptor (CAR) T-cell therapy against MSLN has shown promising results in preclinical models, as well as safety in a phase I trial.
Researchers from Caribou Biosciences Inc. presented preclinical data for the novel BCMA-specific allogeneic CAR T-cell therapy candidate, CB-011, being developed for the treatment of relapsed or refractory multiple myeloma. A genome editing strategy was implemented in the production of CB-011 to blunt CAR T-cell rejection by both patient T cells and natural killer (NK) cells.
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