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Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor

by Wada, M , Lan, F , Jiang, X , Jares, A , Firor, A E , Golightly, M , Lin, K-W , Shuai, X , Leung, E L , Pinz, K G , Liu, H , Salman, H , Senzel, L , Chen, K H , Ma, Y

in 13/106 / 13/31 / 4-1BB Ligand - genetics / 4-1BB Ligand - immunology / 631/250/1904 / 631/250/232 / 631/67/1990 / 64/60 / 692/4028/67/1059/2325 / 692/699/67/1990/283/2125 / 692/699/67/1990/291/1621/1916 / 692/700/1750 / Acute lymphoblastic leukemia / Animal models / Animals / Anticancer properties / Antigens / Antigens, Neoplasm - immunology / Antitumor agents / Blood diseases / Cancer Research / Care and treatment / CD28 Antigens - immunology / CD3 Complex - genetics / CD3 Complex - immunology / CD5 antigen / CD5 Antigens - immunology / CD8 Antigens - immunology / Cell Line, Tumor / Cell receptors / Chimeric antigen receptors / Clinical trials / Coculture Techniques / Critical Care Medicine / Cytotoxicity / Cytotoxicity, Immunologic / Development and progression / Disease control / Genetic aspects / Health aspects / Hematology / Humans / Immunotherapy / Immunotherapy, Adoptive - methods / Innovations / Intensive / Internal Medicine / Killer Cells, Natural - immunology / Killer Cells, Natural - transplantation / Leukemia / Lymphatic leukemia / Lymphocytes B / Lymphocytes T / Lymphoma / Lymphoma, T-Cell, Peripheral - pathology / Lymphoma, T-Cell, Peripheral - therapy / Medical research / Medicine / Medicine & Public Health / Mice / Molecular Targeted Therapy / Natural killer cells / Oncology / Original / original-article / Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology / Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - therapy / Recombinant Fusion Proteins - immunology / Salvage Therapy / Single-Chain Antibodies - genetics / Single-Chain Antibodies - immunology / T cell receptors / T cells / Toxicity / Transduction, Genetic / Tumor cell lines / Tumor cells / Tumor Necrosis Factor Receptor Superfamily, Member 9 - immunology / Xenograft Model Antitumor Assays / Xenografts

2017

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Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor

by Wada, M , Lan, F , Jiang, X , Jares, A , Firor, A E , Golightly, M , Lin, K-W , Shuai, X , Leung, E L , Pinz, K G , Liu, H , Salman, H , Senzel, L , Chen, K H , Ma, Y

2017

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Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor

by Wada, M , Lan, F , Jiang, X , Jares, A , Firor, A E , Golightly, M , Lin, K-W , Shuai, X , Leung, E L , Pinz, K G , Liu, H , Salman, H , Senzel, L , Chen, K H , Ma, Y

2017

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Journal Article

Preclinical targeting of aggressive T-cell malignancies using anti-CD5 chimeric antigen receptor

Wada, M,

Lan, F,

Jiang, X,

Jares, A,

Firor, A E,

Golightly, M,

Lin, K-W,

Shuai, X,

Leung, E L,

Pinz, K G,

Liu, H,

Salman, H,

Senzel, L,

Chen, K H,

Ma, Y

2017

Overview

The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs). Here, we report a robust anti-CD5 CAR (CD5CAR) transduced into a human NK cell line NK-92 that can undergo stable expansion ex vivo. We found that CD5CAR NK-92 cells possessed consistent, specific, and potent anti-tumor activity against a variety of T-cell leukemia and lymphoma cell lines as well as primary tumor cells. Furthermore, we were able to demonstrate significant inhibition and control of disease progression in xenograft mouse models of T-ALL. The data suggest that CAR redirected targeting for T-cell malignancies using NK cells may be a viable method for new and complementary therapeutic approaches that could improve the current outcome for patients.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

13/106

/ 13/31

/ 4-1BB Ligand - genetics

/ 4-1BB Ligand - immunology

/ 631/250/1904

/ 631/250/232

/ 631/67/1990