TY - JOUR
T1 - Production and characterization of haploidentical CD19 CAR T cells
T2 - Validated to induce a continuous complete remission in a patient with relapsed refractory B-cell ALL
AU - Prasongtanakij, Somsak
AU - Anurathapan, Usanarat
AU - Vanichapol, Thitinee
AU - Jittorntrum, Bunyada
AU - Atjanasuppat, Korakot
AU - Pongpitcha, Pongpak
AU - Pakakasama, Samart
AU - Songdej, Duantida
AU - Sirachainan, Nongnuch
AU - Paisooksantivatana, Karan
AU - Borwaornpinyo, Suparerk
AU - Andersson, Borje S.
AU - Hongeng, Suradej
N1 - Publisher Copyright:
© 2020 John Wiley & Sons Australia, Ltd
PY - 2022/2
Y1 - 2022/2
N2 - Aims: The purpose of this study was to design and manufacture CD19 chimeric antigen receptor (CAR)-modified T cells for clinical use in Thailand, as a model for how this technology can be directly applied at individual institutions treating high-risk leukemia patients. Methods: We constructed second-generation CAR T cells expressing CD19 scFV-CD28-CD3ζ with different lengths of the spacer region: full, intermediate, and short length, by using a lentiviral vector. We wanted to determine whether the difference in length of the spacer would affect the cytotoxic potential of the CD19 CAR T cells against the leukemic cells. Results: We found that all constructs of CD19 CAR T cells exhibited a similar level of cytotoxicity against several human lymphoma and leukemia cell lines. For the clinical application, we chose the intermediate length spacer construct CD19 CAR T cells, hypothesizing that the highest transduction efficiency coupled with a slower initial proliferation in vitro might lead to effective leukemic cell kill, yet a lower probability for serious clinical side effects. We then tested the clinical efficacy of our CD19 CAR T cells in one patient with refractory/relapsed acute B-cell lymphoblastic leukemia. This patient indeed had minimal clinical side effects after the CAR T-cell infusion, and he remains in an unmaintained, ongoing complete remission 10+ months after his T-cell treatment. Conclusion: Our CD19 CAR T cells demonstrated efficacies in acute lymphoblastic B-cell leukemia, and will be used to establish an immunotherapeutic program for high-risk B-cell acute lymphoblastic leukemia in Thailand. We propose that this approach can be used as a model for how this new exciting technology can be applied directly at individual institutions that treat (a large number of) patients with high-risk leukemia.
AB - Aims: The purpose of this study was to design and manufacture CD19 chimeric antigen receptor (CAR)-modified T cells for clinical use in Thailand, as a model for how this technology can be directly applied at individual institutions treating high-risk leukemia patients. Methods: We constructed second-generation CAR T cells expressing CD19 scFV-CD28-CD3ζ with different lengths of the spacer region: full, intermediate, and short length, by using a lentiviral vector. We wanted to determine whether the difference in length of the spacer would affect the cytotoxic potential of the CD19 CAR T cells against the leukemic cells. Results: We found that all constructs of CD19 CAR T cells exhibited a similar level of cytotoxicity against several human lymphoma and leukemia cell lines. For the clinical application, we chose the intermediate length spacer construct CD19 CAR T cells, hypothesizing that the highest transduction efficiency coupled with a slower initial proliferation in vitro might lead to effective leukemic cell kill, yet a lower probability for serious clinical side effects. We then tested the clinical efficacy of our CD19 CAR T cells in one patient with refractory/relapsed acute B-cell lymphoblastic leukemia. This patient indeed had minimal clinical side effects after the CAR T-cell infusion, and he remains in an unmaintained, ongoing complete remission 10+ months after his T-cell treatment. Conclusion: Our CD19 CAR T cells demonstrated efficacies in acute lymphoblastic B-cell leukemia, and will be used to establish an immunotherapeutic program for high-risk B-cell acute lymphoblastic leukemia in Thailand. We propose that this approach can be used as a model for how this new exciting technology can be applied directly at individual institutions that treat (a large number of) patients with high-risk leukemia.
KW - CD19
KW - acute lymphoblastic leukemia (ALL)
KW - chimeric antigen receptor (CAR) T cells
KW - cytotoxicity
KW - immunotherapy
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U2 - 10.1111/ajco.13474
DO - 10.1111/ajco.13474
M3 - Article
C2 - 32970928
AN - SCOPUS:85091348722
SN - 1743-7555
VL - 18
SP - 44
EP - 51
JO - Asia-Pacific Journal of Clinical Oncology
JF - Asia-Pacific Journal of Clinical Oncology
IS - 1
ER -