T cell-engaging bispecific antibodies (TCEs) are engineered molecules designed to bring cytotoxic T cells into proximity with tumor cells, triggering a targeted, antigen-dependent immune attack. However, TCE may activate T cells in healthy tissues, leading to off-tumor toxicity.
IL-2 is clinically validated as an immunotherapeutic, but its use is limited by toxicity issues. AZD-6750 is an approach from Astrazeneca plc that applies cis-guiding to deliver a modified IL-2 mutein to CD8+ T cells.
Treatment in glioblastoma usually fails due to tumor heterogeneity and persistence of glioblastoma multiforme stem-like cells (GSCs) within the tumor margin. Researchers from Trogenix Ltd. engineered TGX-007, an AAV1-mediated therapeutic that delivers both cytotoxic and immunomodulatory genetic payloads to the tumor.
HER2-targeted antibody-drug conjugates (ADCs) have significantly improved cancer therapy in recent decades. However, ADCs can cause toxicity and resistance, while T-cell engagers (TCEs) show promising antitumor activity in solid tumors but are limited by substantial adverse effects.
Researchers from Synthekine Inc. presented preclinical efficacy data on STK-012, a first-in-class IL-2 partial agonist engineered for preferential binding to the IL-2Rαβγ receptor.
High-grade gliomas, including glioblastomas, are aggressive cancers of the brain that usually recur despite standard treatment, including radiation therapy. These mechanisms conferring persistence to tumor cells may be explained by DNA damage response pathways, especially those relying on ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK), which induce the repair of radiation-induced DNA damage. The effects of the ATM/DNA-PK inhibitor XRD-0394 were evaluated in in vitro models of glioma.
Pancreatic cancer is among the most aggressive cancer types, with survival rates being very low and current treatment being quite ineffective. To address this unmet medical need, HCW Biologics Inc. has developed and presented preclinical data for their T-cell engager approach – HCW11-018.
M-3554 is an antibody-drug conjugate (ADC) targeting GD2; it has shown strong antitumor activity in neuroblastoma xenograft models and has been engineered to reduce anti-GD2 antibody-associated pain.
Vivace Therapeutics Inc. reported preclinical efficacy data of VT-3989, a TEAD inhibitor, in in vitro and in vivo models of aggressive meningioma. VT-3989 is in early clinical development for the treatment of patients with advanced solid tumors.
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