Donor T cells for CAR T cell therapy

Tiffany C Y Tang; Ning Xu; Robert Nordon; Michelle Haber; Kenneth Micklethwaite; Alla Dolnikov

doi:10.1186/s40364-022-00359-3

Donor T cells for CAR T cell therapy

Biomark Res. 2022 Apr 1;10(1):14. doi: 10.1186/s40364-022-00359-3.

Authors

Tiffany C Y Tang^{1

2}, Ning Xu^{3

4}, Robert Nordon⁵, Michelle Haber^{3

4

6}, Kenneth Micklethwaite^{7

8

9

10}, Alla Dolnikov^{3

4

6}

Affiliations

¹ Graduate School of Biomedical Engineering, Faculty of Engineering, UNSW Sydney, Sydney, NSW, Australia. [email protected].
² Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, Sydney, NSW, Australia. [email protected].
³ Children's Cancer Institute, Lowy Cancer Research Center, UNSW Sydney, Sydney, NSW, Australia.
⁴ School of Women's and Children's Health, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
⁵ Graduate School of Biomedical Engineering, Faculty of Engineering, UNSW Sydney, Sydney, NSW, Australia.
⁶ Kids Cancer Center, Sydney Children's Hospital, Sydney, NSW, Australia.
⁷ Blood Transplant and Cell Therapies Program, Department of Hematology, Westmead Hospital, Sydney, NSW, Australia.
⁸ Blood Transplant and Cell Therapies Laboratory, NSW Health Pathology, ICPMR Westmead, Sydney, NSW, Australia.
⁹ Westmead Institute for Medical Research, Sydney, NSW, Australia.
¹⁰ Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Abstract

Adoptive cell therapy using patient-derived chimeric receptor antigen (CAR) T cells redirected against tumor cells has shown remarkable success in treating hematologic cancers. However, wider accessibility of cellular therapies for all patients is needed. Manufacture of patient-derived CAR T cells is limited by prolonged lymphopenia in heavily pre-treated patients and risk of contamination with tumor cells when isolating T cells from patient blood rich in malignant blasts. Donor T cells provide a good source of immune cells for adoptive immunotherapy and can be used to generate universal off-the-shelf CAR T cells that are readily available for administration into patients as required. Genome editing tools such as TALENs and CRISPR-Cas9 and non-gene editing methods such as short hairpin RNA and blockade of protein expression are currently used to enhance CAR T cell safety and efficacy by abrogating non-specific toxicity in the form of graft versus host disease (GVHD) and preventing CAR T cell rejection by the host.

Keywords: CRISPR-Cas9; Donor CAR T cells; GVHD; Genome editing; TALENs.

Publication types

Review

Abstract

Publication types

Grants and funding