CXCR1- or CXCR2-modified CAR T Cells Co-opt IL-8 for Maximal Antitumor Efficacy in Solid Tumors

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Sep 7

PMID 31488817

Citations 186

Authors

Linchun Jin

Haipeng Tao

Aida Karachi

Yu Long

Alicia Y Hou

Meng Na

Kyle A Dyson

Adam J Grippin

Loic P Deleyrolle

Wang Zhang

Didier A Rajon

Qiong J Wang

James C Yang

Jesse L Kresak

Elias J Sayour

Maryam Rahman

Frank J Bova

Zhiguo Lin

Duane A Mitchell

Jianping Huang

Affiliations

Soon will be listed here.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy targeting solid tumors has stagnated as a result of tumor heterogeneity, immunosuppressive microenvironments, and inadequate intratumoral T cell trafficking and persistence. Early (≤3 days) intratumoral presentation of CAR T cells post-treatment is a superior predictor of survival than peripheral persistence. Therefore, we have co-opted IL-8 release from tumors to enhance intratumoral T-cell trafficking through a CAR design for maximal antitumor activity in solid tumors. Here, we demonstrate that IL-8 receptor, CXCR1 or CXCR2, modified CARs markedly enhance migration and persistence of T cells in the tumor, which induce complete tumor regression and long-lasting immunologic memory in pre-clinical models of aggressive tumors such as glioblastoma, ovarian and pancreatic cancer.

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