Delving into the Latest Updates on GD2-B7H3 SynNotch CAR-T with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms-

Target

CD276 x GD2

Action

modulators

Mechanism

CD276 modulators(CD276 antigen modulators), GD2 modulators(Disialoganglioside GD2 modulators)

Therapeutic Areas

NeoplasmsOther Diseases

Active Indication-

Inactive Indication

Neuroblastoma

Originator Organization

Children's Hospital Los Angeles

Active Organization-

Inactive Organization

Children's Hospital Los Angeles

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

AbstractThe ability to utilize preclinical models to predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating the development and evaluation of gated systems. Here we found that murine GD2 CAR-T cells, specific for the tumor-associated antigen GD2, induce fatal neurotoxicity in a costimulatory domain-dependent manner. Meanwhile, human B7H3 CAR-T cells exhibit efficacy in preclinical models of neuroblastoma. Seeking a better CAR, we generated a SynNotch gated CAR-T, GD2-B7H3, recognizing GD2 as the gate and B7H3 as the target. GD2-B7H3 CAR-T cells control the growth of neuroblastoma in vitro and in metastatic xenograft mouse models, with high specificity and efficacy. These improvements come partly from the better metabolic fitness of GD2-B7H3 CAR-T cells, as evidenced by their naïve T-like post-cytotoxicity oxidative metabolism and lower exhaustion profile.

100 Deals associated with GD2-B7H3 SynNotch CAR-T

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