Limited data exist on checkpoint inhibition that targets the early activation phase of adaptive immunity. B-and T-lymphocyte attenuator (BTLA) blockade is known to enhance and broaden CD8+ T-cell responses to a target antigen.
Researchers from Memorial Sloan Kettering Cancer Center and affiliated organizations presented data from a study that aimed to investigate the immunomodulatory functions of lysine-specific demethylase 1 (LSD1) in regulating MHC-I antigen presentation pathway (APP) and resistance to immunotherapy in patients with small-cell lung cancer (SCLC).
CD73 is known to induce immune evasion in solid tumors by release of immune-suppressive adenosine in the tumor microenvironment. Researchers from Cidara Therapeutics Inc. have presented preclinical data on the CD73 inhibitor drug FC-conjugate CBO-212 for the potential treatment of solid tumors.
Molecular Templates Inc. has received IND clearance from the FDA for its novel MT-8421 engineered toxin bodies (ETB) program targeting cytotoxic T-lymphocyte protein 4 (CTLA-4) in patients with relapsed/refractory solid tumors previously exposed to checkpoint inhibitors. MT-8421 is designed to eliminate CTLA-4-expressing regulatory T cells (Tregs) in the tumor microenvironment (TME) through a direct cell-kill mechanism independent of the effector cell presence that antibodies rely upon while not affecting Tregs in the periphery.
A deficiency in fumarate metabolism could be behind a new mechanism of inflammation mediated by mitochondrial DNA and RNA. Two independent and simultaneous studies described how the accumulation of fumarate in the mitochondria released the genetic material of this organelle through vesicles, activating an inflammatory signaling pathway.
Estrella Biopharma Inc. has received FDA clearance of its IND application for lead product candidate EB-103, a T-cell therapy targeting CD19, a protein expressed on the surface of almost all B-cell leukemias and lymphomas.
Researchers from the Brigham and Women’s Hospital and Harvard Medical School and collaborators recently conducted a study investigating the regulation of immune checkpoint molecules in cancer. Analyzing data from The Cancer Genome Atlas pan-cancer cohort (over 10,000 patients and 11,000 samples across 34 different cancer subtypes), they found that high expression of the immune checkpoint B7-H3 (CD276) and high mTORC1 activity correlate with immunosuppressive phenotypes and worse clinical outcomes.