Delving into the Latest Updates on B7-H3.CAR-Ts with Synapse

Overview

Basic Info

Drug Type

Universal CAR-T

Synonyms

Target

CD276 x PDL1

Action

inhibitors

Mechanism

CD276 inhibitors(CD276 antigen inhibitors), PDL1 inhibitors(Programmed death-ligand 1 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [2]

Active Indication

NeuroblastomaOvarian CancerPancreatic Cancer

Inactive Indication-

Originator Organization

University of North Carolina System

Active Organization

University of North Carolina System

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Ferrone, Cristina Rosa ; Montgomery, Stephanie Ann ; Pylayeva-Gupta, Yuliya ; Ferrone, Soldano ; Chen, Yuhui ; Ahn, Sarah ; Dotti, Gianpietro ; Tiruthani, Karthik ; Du, Hongwei ; Hirabayashi, Koichi ; Sun, Chuang ; Kren, Nancy Porterfield ; Xu, Yang ; Liu, Rihe ; Greene, Kevin ; Mirlekar, Bhalchandra ; Yeh, Jen Jen ; Ma, Xingcong ; Michaud, Daniel ; Herrera, Silvia Gabriela ; Savoldo, Barbara ; Wang, Xinhui

The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. We also found that 4-1BB co-stimulation promotes lower PD-1 expression in B7-H3.CAR-Ts, and superior antitumor activity when targeting tumor cells that constitutively expressed PD-L1. We took advantage of the cross-reactivity of the B7-H3.CAR with murine B7-H3, and found that B7-H3.CAR-Ts significantly controlled tumor growth in a syngeneic tumor model without evident toxicity. These findings support the clinical development of B7-H3.CAR-Ts.

100 Deals associated with B7-H3.CAR-Ts

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuroblastoma	Preclinical	United States	University of North Carolina System	11 Feb 2019
Ovarian Cancer	Preclinical	United States	University of North Carolina System	11 Feb 2019
Pancreatic Cancer	Preclinical	United States	University of North Carolina System	11 Feb 2019