Immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer management. However, acquired resistance and response variability point to rational combination strategies as the goal to achieve significant improvements in the field. Investigators at the National Cancer Center of Japan have found that stimulators of the innate immune response unexpectedly activated suppressive cells of the innate immune system.
The tumor microenvironment plays a crucial role in the resistance of solid tumors to immunotherapy. In particular, fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts have been shown to contribute to immune evasion.
Stimulating the body’s immune defenses against a tumor can reduce or eliminate it. However, in cancer immunotherapy, when immune checkpoint inhibitors unleash the immune system, severe autoimmunity can result. A hematological technique, extracorporeal photopheresis (ECP), could offer a solution. It reduces the therapy-induced inflammation without altering antitumor immunity. According to scientists at the Universities of Basel and Freiburg, the key lies in adiponectin, a hormone produced by fatty tissue.
Work at Exelixis Inc. has led to the development of antibody-drug conjugates (ADCs) comprising antibodies targeting interleukin-13 receptor subunit α2 (IL-13RA2, IL-13R-α2) covalently linked to a payload. They are described as potentially useful for the treatment of non-small-cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC).
Xilio Therapeutics Inc. has announced three wholly owned preclinical programs for masked T-cell engagers targeting prostate-specific membrane antigen (PSMA), claudin 18.2 (CLDN18.2) and six-transmembrane epithelial antigen of prostate 1 (STEAP1).
Within the immune system, interleukin-15 (IL-15) plays a relevant role by boosting the number of cytotoxic T cells and NK cells, the major drivers of anticancer immune response. Researchers from Sotio Biotech AS, MD Anderson and collaborators reported preclinical data on nanrilkefusp alfa (nanril; SOT-101), an IL-15 receptor βγ superagonist that stimulates both CD8+ T and NK cells in the tumor microenvironment.
Ellipses Pharma Ltd. has agreed to in-license global rights to GENA-104, a first-in-class immuno-oncology monoclonal antibody that targets CNTN4, from Genome & Co. Ltd. Targeting CNTN4 is a new approach that blocks the CNTN4-APP checkpoint interaction on T cells, promoting tumor cell killing, with potential use in cancers that respond poorly to conventional checkpoint inhibitors.
Bioray Pharmaceutical Co. Ltd. has announced clinical trial clearance in China by the National Medical Products Administration (NMPA) for BR-111 for injection for the treatment of ROR1-positive hematological malignancies and solid tumors.
Leukemic stem cells (LSCs) and stemness signatures contribute to minimal residual disease in patients with acute myeloid leukemia (AML), which is associated with an increased risk of relapse. The presence of LSCs predicts treatment success and, therefore, eliminating LSCs has been proposed as a promising strategy to avoid relapses.
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