Delving into the Latest Updates on STEAP1 Targeted CAR-T(FredHutch) with Synapse

Overview

Basic Info

Drug Type

CAR-T

Synonyms-

Target

Mechanism

IL-12R modulators(IL-12 receptor modulators), STEAP1 modulators(Six-transmembrane epithelial antigen of the prostate 1 modulators)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostatic Cancer

Inactive Indication-

Originator Organization

Fred Hutchinson Cancer Research Center

Active Organization

Fred Hutchinson Cancer Research Center

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Rudoy, Dmytro ; Zhang, Ailin ; Wu, Li-Ting ; Tsao, Annabelle ; Haffner, Michael C ; Lee, John K ; Ishihara, Jun ; Nutt, Sam ; Pariva, Tiffany E ; Patel, Radhika A ; True, Lawrence D ; Roudier, Martine P ; Nelson, Peter S ; Priceman, Saul J ; Kamat, Nikhil V ; Morrissey, Colm M ; Gulati, Roman ; Bhatia, Vipul ; Coleman, Ilsa ; Sasaki, Koichi ; Sun, Huiyun ; Hitchcock, Lauren ; Srivastava, Shivani ; Javier, Gerardo

AbstractSix transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen for therapeutic targeting in prostate cancer. Here, we report broad expression of STEAP1 relative to prostate-specific membrane antigen (PSMA) in lethal metastatic prostate cancers and the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrate reactivity in low antigen density, antitumor activity across metastatic prostate cancer models, and safety in a human STEAP1 knock-in mouse model. STEAP1 antigen escape is a recurrent mechanism of treatment resistance and is associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein combined with STEAP1 CAR T cell therapy enhances antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading.

100 Deals associated with STEAP1 Targeted CAR-T(FredHutch)

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