Calidi Biotherapeutics Inc. recently presented data regarding CLD-401 as an immunotherapeutic approach developed using the Redtail gene therapy platform. This platform uses a tumor-specific, replicating enveloped vaccinia virus that expresses a chimeric form of CD55 to allow complement and neutralizing antibody resistance, as well as systemic administration.
Mitogen-activated protein kinase kinase kinase kinase 1 (HPK1) is a serine/threonine protein kinase that is expressed in the hematopoietic compartment, exerting regulatory functions in myeloid and innate immune cells. It has been associated with decreased T-cell activation and proliferation.
CD137 is a potent immune costimulatory receptor that promotes T-cell activation and enhances antitumor immune responses. However, systemic activation of CD137 can result in excessive immune stimulation and associated safety risks, such as hepatotoxicity, limiting its clinical use.
Researchers from Agni Bio Inc. reported the preclinical profile of AGB-201, a bispecific antibody designed to simultaneously target EDB and LTβR, while minimizing unwanted immune activation.
At the ongoing AACR Immuno-Oncology Conference (AACR IO) in Los Angeles, Ampersand Biomedicines Inc. gave a presentation on promising results in the field regarding AMP-410, an anti-VEGF/4-1BB antibody construct that limits 4-1BB activation in VEGF-rich tumor types, thus achieving durable efficacy.
Epimab Biotherapeutics Inc. licensed out a development-ready KLK2/CD3 bispecific T-cell engager (TCE) for advanced prostate cancer to Juri Biosciences Inc. through a potential $210 million deal.
Tissue factor (TF), a transmembrane protein overexpressed in tumors such as cervical, head and neck, NSCLC, and pancreatic cancers, initiates the extrinsic coagulation pathway under normal subendothelial expression. TF-targeted vedotin antibody-drug conjugates (ADCs) are in clinical evaluation for solid tumors, but toxicities, including peripheral neuropathy, ocular effects and epistaxis, limit their use.
Tumors with high levels of microsatellite instability (MSI-H), such as some subsets of colorectal, endometrial and gastric cancers, are associated with a hypermutated phenotype and a specific dependency on the WRN gene. Pharmacologic inhibition of WRN has been shown to selectively impair the viability of MSI-H cancer cells, effectively blocking tumor growth while sparing microsatellite-stable (MSS) cells.
About 15% of all cancers have co-deletion of both the MTAP and CDKN2A genes, which results in sensitization to MAT2A inhibitors, thus opening a therapeutic window in these cancer types. MAT2A inhibitors have demonstrated efficacy in MTAD-deficient cancers. Shouyao Holdings (Beijing) Co. Ltd. has developed and released data for their MAT2A inhibitor SY-9453 for the treatment of MTAP-deficient cancers.
Peptide-drug conjugates (PDCs) are emerging as a promising alternative to antibody-drug conjugates (ADCs), offering enhanced tumor penetration and reduced immunogenicity. Carbonic anhydrase IX (CAIX) and epidermal growth factor receptor (EGFR) are both well-validated targets in oncology due to their role in cancer cell survival, invasion and migration.
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