Off the shelf T cell therapies for hematologic malignancies

Bruce J McCreedy; Vladimir V Senyukov; Kim T Nguyen

doi:10.1016/j.beha.2018.03.001

Off the shelf T cell therapies for hematologic malignancies

Best Pract Res Clin Haematol. 2018 Jun;31(2):166-175. doi: 10.1016/j.beha.2018.03.001. Epub 2018 Mar 28.

Authors

Bruce J McCreedy¹, Vladimir V Senyukov², Kim T Nguyen³

Affiliations

¹ Precision BioSciences, Inc., 302 East Pettigrew Street, Durham, NC 27701, USA. Electronic address: bruce.mccreedy@precisionbiosciences.com.
² Precision BioSciences, Inc., 302 East Pettigrew Street, Durham, NC 27701, USA. Electronic address: vladimir.senyukov@precisionbiosciences.com.
³ Precision BioSciences, Inc., 302 East Pettigrew Street, Durham, NC 27701, USA. Electronic address: kim.nguyen@precisionbiosciences.com.

PMID: 29909917
DOI: 10.1016/j.beha.2018.03.001

Abstract

Adoptive transfer of autologous CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies. However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity. Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients. Additional gene edits can be included to impart resistance to immunosuppression or improve trafficking to tumor sites. Recent advances in cell manufacturing and analytics technology can provide for consistent batch to batch manufacturing of gene edited allogeneic CAR-T cells in sufficient quantity to treat thousands of patients when needed as off the shelf products.

Keywords: Allogeneic; CAR-T cells; Gene editing.

Publication types

Review

MeSH terms

Gene Editing
Graft vs Host Disease / genetics
Graft vs Host Disease / immunology
Graft vs Host Disease / pathology
Graft vs Host Disease / prevention & control
Hematologic Neoplasms* / genetics
Hematologic Neoplasms* / immunology
Hematologic Neoplasms* / pathology
Hematologic Neoplasms* / therapy
Humans
Immunosuppression Therapy / methods*
Immunotherapy, Adoptive / methods*
Receptors, Chimeric Antigen* / genetics
Receptors, Chimeric Antigen* / immunology
Receptors, Chimeric Antigen* / therapeutic use
T-Lymphocytes* / immunology
T-Lymphocytes* / pathology
T-Lymphocytes* / transplantation

Substances

Receptors, Chimeric Antigen