Activation of the cGAS-STING pathway activates the immune system through the production of type I interferons. There is knowledge that myeloid cell populations are among the most sensitive to STING agonism. Investigators at Takeda Pharmaceutical Co. Ltd. presented results on TAK-500, an immune stimulant antibody-drug conjugate (ISAC) composed of an antibody linked to a STING agonist for delivery to CCR2+ cells.
A combination of radiation therapy and CD47 blockade induced an abscopal effect in animal studies even in animals that lacked T cells, researchers reported in the Nov. 21, 2022, online issue of Nature Cancer. The findings are “the first demonstration of T-cell-independent abscopal response,” co-corresponding author Edward Graves told BioWorld. “We’re not trying to say that all abscopal responses are macrophage-mediated. There are plenty that require T cells,” Graves clarified. But “there is another avenue of abscopal responses that has not been reported. ... All the abscopal literature is about stimulating an adaptive response.”
Researchers from Elpiscience Biopharma Ltd. have reported the construction of a PD-L1/SIRPα bispecific macrophage engager (BiME), ES-019. A panel of anti-PD-L1/SIRPα antibodies based on single domain antibody was generated, with the candidates containing different orientations, ratios and IgG isotypes of anti-PD-L1 arm and anti-SIRPα arm.
Immunocytokines (ICs) engage multiple mechanisms of action by the use of antibodies to deliver cytokine payloads to the surface of the same immune cell, known as cis-signaling. Researchers from Bright Peak Therapeutics AG have developed ICs by using a novel approach based on site-specific chemical conjugation of engineered cytokines to existing nonmodified antibodies.
Umoja Biopharma Inc. and Nanjing Iaso Biotherapeutics Co. Ltd. have entered into a research agreement to evaluate Umoja's ICIL (induced cytotoxic innate lymphocytes) platform with Iaso's best-in-class chimeric antigen receptors (CARs).
Sensei Biotherapeutics Inc. has entered into a sponsored research agreement with Washington University in St. Louis to support development of SNS-101, a conditionally active V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA)-blocking antibody.
Investigators at the École Polytechnique Fédérale de Lausanne (EPFL; Swiss Federal Institute of Technology Lausanne) have identified a broad role for the fragile X mental retardation protein (FMRP) in suppressing antitumor immunity, they reported in the Nov. 18, 2022, issue of Science. The results could lead to new ways to boost antitumor immunity. Scientifically, they also provide new insights into the link between tumors and the nervous system.
Mutations in FMR1, the gene that codes for FMRP, cause fragile X syndrome, a neurodevelopmental syndrome that is characterized by mental retardation and autism-like symptoms.Previous work in the laboratory of Douglas Hanahan, who is the senior author of the Science paper, as well as by other teams had shown that FMRP levels were increased in several tumor types, and increased the chances that those tumors would metastasize.
Researchers from Carisma Therapeutics Inc. have provided details on the discovery and preclinical evaluation of a novel mesothelin-targeting chimeric antigen receptor macrophage (CAR-M), CT-1119, being developed as a potential solid tumor immunotherapy candidate.
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