Preclinical and clinical studies of CAR-NK-cell therapies for malignancies

Abstract

The development of chimeric antigen receptor T (CAR-T) cell therapy, a specific type of immunotherapy, in recent decades was a fantastic breakthrough for the treatment of hematological malignancies. However, difficulties in collecting normal T cells from patients and the time cost of manufacturing CAR-T cells have limited the application of CAR-T-cell therapy. In addition, the termination of related clinical trials on universal CAR-T cell therapy has made further research more difficult. Natural killer (NK) cells have drawn great attention in recent years. Chimeric antigen receptor-NK (CAR-NK) cell therapy is a promising strategy in the treatment of malignant tumors because of its lack of potential for causing graft-versus-host disease (GVHD). In this review, we will address the advances in and achievements of CAR-NK cell therapy.

Antitumor activity of genetically engineered NK-cells in non-hematological solid tumor: a comprehensive review

“…Commonly used transmembrane components for CAR-NK cells are modified from CD3ζ, CD8, and CD28, with others like NKG2D, 2B4, and DNAM1 also under investigation. The intracellular signaling domain primarily comprises the CD3ζ chain of the T-cell receptor (TCR) as a signaling domain, along with costimulatory molecules ( 20 , 27 , 28 ). Different generations of CARs result from changes to the intracellular signal transduction domain ( 29 ).…”

Umbilical cord blood and cord tissue banking as somatic stem cell resources to support medical cell modalities

“…Although the use of CB for hematopoietic stem cell transplantation has decreased recently in the world [ 1 ], new technologies have promoted the use of expanded CD34 + cells for HSCT [ 25 ], regulatory T cells to induce tolerance in HSCT [ 26 , 27 ], universal chimeric antigen receptor-T cell therapy (CAR-T) [ 28 ], and universal CAR-NK cells [ 29 – 32 ] for hematological malignancies.…”

Breaking down barriers: The potential of smarter CAR‐engineered NK cells against solid tumors

“…78 Most of the CAR-NK cells have been analyzed for their immunotherapeutic abilities in Patient-derived xenografts (PDX) model in preclinical studies such as CAR redirected against different hematological tumor targets such as CD19, CD20, CD138, and CS-1 as well as for solid tumors including HER2, PSCA, GD2, and EG. 79 Furthermore, the humanized mice are considered even more precise models than PDX and are created by the transplantation of potent human hematopoietic stem cells (HSCs) into immune-deficient mice, thus allowing it to develop human immunity within its body that controls the failure of PDX model to evaluate the effect of CAR-NK/T complex on the host cells in the tumor microenvironment (TME). 80 In this preclinical trial, CD44v6-CAR-T cells were then transplanted into the humanized mice to inspect their on-or-off target tumor toxicity to HSCs.…”

“…Interestingly, the patient‐derived tumor xenograft (PDX) model persists heterogeneity of the primary tumors and hence serves as an excellent clinical model for cancer treatment as it can directly transfer the tumors from patients to NSG or NOG (with IL2RG mutation) mice 78 . Most of the CAR‐NK cells have been analyzed for their immunotherapeutic abilities in Patient‐derived xenografts (PDX) model in preclinical studies such as CAR redirected against different hematological tumor targets such as CD19, CD20, CD138, and CS‐1 as well as for solid tumors including HER2, PSCA, GD2, and EG 79 . Furthermore, the humanized mice are considered even more precise models than PDX and are created by the transplantation of potent human hematopoietic stem cells (HSCs) into immune‐deficient mice, thus allowing it to develop human immunity within its body that controls the failure of PDX model to evaluate the effect of CAR‐NK/T complex on the host cells in the tumor microenvironment (TME) 80 .…”