Probiotic-guided CAR-T cells for solid tumor targeting

被引：136

作者：

Vincent, Rosa L. ^{[1
]}

Gurbatri, Candice R. ^{[1
]}

Li, Fangda ^{[2
]}

Vardoshvili, Ana ^{[1
]}

Coker, Courtney ^{[1
]}

Im, Jongwon ^{[1
]}

Ballister, Edward R. ^{[1
,2
]}

Rouanne, Mathieu ^{[2
,3
]}

Savage, Thomas ^{[2
]}

de los Santos-Alexis, Kenia ^{[2
]}

Redenti, Andrew ^{[2
]}

Brockmann, Leonie ^{[2
]}

Komaranchath, Meghna ^{[1
]}

Arpaia, Nicholas ^{[2
,3
]}

Danino, Tal ^{[1
,3
,4
]}

机构：

[1] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA

[2] Columbia Univ, Dept Microbiol & Immunol, Vagelos Coll Phys & Surg, New York, NY 10032 USA

[3] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[4] Columbia Univ, Data Sci Inst, New York, NY 10027 USA

来源：

SCIENCE | 2023年 / 382卷 / 6667期

关键词：

CHIMERIC ANTIGEN RECEPTORS; PHASE-I; AFFINITY; TLR5;

D O I：

10.1126/science.add7034

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)-T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ. This system demonstrated CAR-T cell activation and antigen-agnostic cell lysis that was safe and effective in multiple xenograft and syngeneic models of human and mouse cancers. We further engineered multifunctional probiotics that co-release chemokines to enhance CAR-T cell recruitment and therapeutic response.

引用

页码：211 / 218

页数：8

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