Engineering Axl specific CAR and SynNotch receptor for cancer therapy

Scientific Reports
Jang Hwan ChoWilson W Wong

Abstract

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 reage...Continue Reading

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Citations

Nov 15, 2019·HemaSphere·Astrid Holzinger, Hinrich Abken
May 1, 2020·Cytometry. Part B, Clinical Cytometry·Elena MaryamchikMarcela V Maus
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Apr 4, 2021·Molecular Cancer Research : MCR·Wenting DuRolf A Brekken

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Methods Mentioned

BETA
flow cytometry
xenograft
transfection

Software Mentioned

SynNotch
Axl

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