Targeting Tumor-Associated Sialic Acids Using Chimeric Switch Receptors Based on Siglec-9 Enhances the Antitumor Efficacy of Engineered T Cells.

Cancer exploits different mechanisms to escape T-cell immunosurveillance, including overexpression of checkpoint ligands, secretion of immunosuppressive molecules, and aberrant glycosylation. Herein, we report that IFNγ, a potent immunomodulator secreted in the tumor microenvironment, can induce α2,6 hypersialylation in cancer cell lines derived from various histologies. We focused on Siglec-9, a receptor for sialic acid moieties, and demonstrated that the Siglec-9+ T-cell population displayed reduced effector function.

Genetically engineering glycolysis in T cells increases their antitumor function.

Background: T cells play a central role in the antitumor response. However, they often face numerous hurdles in the tumor microenvironment, including the scarcity of available essential metabolites such as glucose and amino acids. Moreover, cancer cells can monopolize these resources to thrive and proliferate by upregulating metabolite transporters and maintaining a high metabolic rate, thereby outcompeting T cells.

A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function.

Background: Tumors can employ different mechanisms to evade immune surveillance and function. Overexpression of co-inhibitory ligands that bind to checkpoint molecules on the surface of T-cells can greatly impair the function of latter. TIGIT (T cell immunoreceptor with Ig and ITIM domains) is such a co-inhibitory receptor expressed by T and NK cells which, upon binding to its ligand (e.

T-cells "à la CAR-T(e)" - Genetically engineering T-cell response against cancer.

The last decade will be remembered as the dawn of the immunotherapy era during which we have witnessed the approval by regulatory agencies of genetically engineered CAR T-cells and of checkpoint inhibitors for cancer treatment. Understandably, T-lymphocytes represent the essential player in these approaches. These cells can mediate impressive tumor regression in terminally-ill cancer patients.

Targeting Multiple Tumors Using T-Cells Engineered to Express a Natural Cytotoxicity Receptor 2-Based Chimeric Receptor.

Recent developments in cancer treatment are demonstrating the increasing and powerful potential of immunotherapeutic strategies. In this regard, the adoptive transfer of tumor-specific T-lymphocytes approaches can lead to tumor regression in cancer patients. More recently, the use of T-cells genetically engineered to express cancer-specific receptors such as the anti-CD19 chimeric antigen receptor (CAR) continues to show promise for the treatment of hematological malignancies.