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Ref Type Journal Article
PMID (29497107)
Authors Cho JH, Okuma A, Al-Rubaye D, Intisar E, Junghans RP, Wong WW
Title Engineering Axl specific CAR and SynNotch receptor for cancer therapy.
Journal Scientific reports
Vol 8
Issue 1
Date 2018 Mar 01
URL
Abstract Text Axl is a tyrosine kinase receptor that is commonly overexpressed in many cancers. As such, Axl represents an attractive therapeutic target. The transfer of engineered T cell expressing chimeric antigen receptor (CAR) is an exciting cancer therapeutic approach that shows high efficacy against cancers in clinical trials, especially for B cell malignancies. Furthermore, recently developed synthetic Notch (synNotch) receptor has demonstrated potential in enhancing the specificity of CAR T cell therapy and delivering therapeutic payloads to tumors in an antigen-dependent manner. Therefore, a CAR or synNotch against Axl could be a valuable therapeutic reagent against many cancers. Here, we develop a single-chain variable fragment from a humanized monoclonal antibody against Axl. The scFv is attached to CD3ζ, CD28, and 4-1BB signaling domains to generate an anti-Axl CAR. When introduced into human primary T cells, the anti-Axl CAR can lead to cytokine production and cell killing in response to tumor cells expressing Axl. Moreover, an anti-Axl synNotch generated using the same scFv can be activated with Axl expressing tumor cells. Given the fact that Axl is an important cancer therapeutic target, these receptors could be valuable reagents for developing anti-Axl therapies.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AXL CAR-T cells AXL CAR-T cells 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
AXL CAR-T cells AXL CAR-T cells are T-cells that are modified to express a chimeric antigen receptor recognizing AXL, which may result in increased death of AXL-expressing tumor cells upon infusion (PMID: 29497107).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References