Delving into the Latest Updates on HER2/IL-13Rα2-bispecific T cell (Baylor College of Medicine) with Synapse

Overview

Basic Info

Drug Type

Autologous CAR-T

Synonyms-

Target

Mechanism

HER2 antagonists(Receptor protein-tyrosine kinase erbB-2 antagonists), IL-13Rα2 modulators(Interleukin-13 receptor subunit alpha-2 modulators)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases

Active Indication

Glioblastoma

Inactive Indication-

Originator Organization

Baylor College of Medicine

Active Organization

Baylor College of Medicine

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractBackgroundChimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.MethodsWe engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant. Bispecific IL-13Rα2/TGF-β CAR-T cells were evaluated for efficacy and safety against both patient-derived GBM xenografts and syngeneic models of murine glioma.ResultsTreatment with IL-13Rα2/TGF-β CAR-T cells leads to greater T-cell infiltration and reduced suppressive myeloid cell presence in the tumor-bearing brain compared to treatment with conventional IL-13Rα2 CAR-T cells, resulting in improved survival in both patient-derived GBM xenografts and syngeneic models of murine glioma.ConclusionsOur findings demonstrate that by reprogramming tumor-specific T-cell responses to TGF-β, bispecific IL-13Rα2/TGF-β CAR-T cells resist and remodel the immunosuppressive TME to drive potent anti-tumor responses in GBM.

100 Deals associated with HER2/IL-13Rα2-bispecific T cell (Baylor College of Medicine)

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