Killer cell immunoglobulin-like receptor 3DL3 (KIR3DL3) is a member of the killer cell Ig-like (KIR) receptor family. When KIR3DL3 is expressed on T and natural killer (NK) cells in the tumor microenvironment, it suppresses immune responses following engagement with HHLA2, suggesting that the KIR3DL3-HHLA2 axis potentially represents a novel immune checkpoint pathway and that blockade of KIR3DL3 signaling could promote antitumor immunity.
Investigators from Immunos Therapeutics AG aimed to develop novel anticancer therapies by using a reverse rational approach from HLA class I molecules with the aim to induce autoimmunity, and they identified HLA-B*57 as a well-known genetic factor associated with superior control of viral infections through processes not linked with peptide presentation.
Treatment with anti-PD-1 checkpoint inhibitors is not effective in all cases, and around 10% of melanoma patients actually experience a rapid deterioration, a phenomenon known as hyperprogressive disease. Some studies have linked hyperprogression to specific immune cell populations or genes, and it remains unclear if this complication can be directly attributed to checkpoint immunotherapy or not.
Jiangsu Mabwell Health Pharmaceutical R&D Co. Ltd. and Mabwell (Shanghai) Bioscience Co. Ltd. have synthesized antibody-drug conjugates (ADCs) consisting of antibodies targeting nectin-4 covalently linked to cytotoxic drugs through a linker reported to be useful for treatment of cancer.
Glioblastoma (GBM) is the most common type of primary brain tumor in adults, with only a 7% rate of 5-year overall survival for patients. Oncolytic viruses based on HSV-1 vectors are an interesting and to-explore area for GBM treatment.
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).
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