Engineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors

被引:153
作者
Sloas, Christopher [1 ]
Gill, Saar [2 ]
Klichinsky, Michael [1 ]
机构
[1] Carisma Therapeut, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA
关键词
CAR (chimeric antigen receptor); solid tumor; adoptive cell immunotherapy; synthetic biology; macrophage; monocyte; MONOCYTE-DERIVED MACROPHAGES; PHASE-I TRIAL; MYELOID CELLS; KILLER-CELLS; T-CELLS; CANCER; RECEPTOR; SYSTEM; EXPRESSION; TARGET;
D O I
10.3389/fimmu.2021.783305
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cellular immunotherapies represent a promising approach for the treatment of cancer. Engineered adoptive cell therapies redirect and augment a leukocyte's inherent ability to mount an immune response by introducing novel anti-tumor capabilities and targeting moieties. A prominent example of this approach is the use of T cells engineered to express chimeric antigen receptors (CARs), which have demonstrated significant efficacy against some hematologic malignancies. Despite increasingly sophisticated strategies to harness immune cell function, efficacy against solid tumors has remained elusive for adoptive cell therapies. Amongst cell types used in immunotherapies, however, macrophages have recently emerged as prominent candidates for the treatment of solid tumors. In this review, we discuss the use of monocytes and macrophages as adoptive cell therapies. Macrophages are innate immune cells that are intrinsically equipped with broad therapeutic effector functions, including active trafficking to tumor sites, direct tumor phagocytosis, activation of the tumor microenvironment and professional antigen presentation. We focus on engineering strategies for manipulating macrophages, with a specific focus on CAR macrophages (CAR-M). We highlight CAR design for macrophages, the production of CAR-M for adoptive cell transfer, and clinical considerations for their use in treating solid malignancies. We then outline recent progress and results in applying CAR-M as immunotherapies. The recent development of engineered macrophage-based therapies holds promise as a key weapon in the immune cell therapy armamentarium.
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页数:10
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