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T-Cell Therapeutics: Donor Lymphocyte Infusion, Cytotoxic T-Lymphocyte Infusion, and Other Non-CAR T-Cell Therapies

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Blood and Marrow Transplant Handbook

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Abstract

Cellular therapy is an integral part of cancer immunotherapy, which is now considered as the fourth pillar of cancer treatment after surgery, chemotherapy, and radiotherapy. Allogeneic hematopoietic cell transplantation (HCT) is considered the most classic example of cellular immunotherapy. Post-transplant interplay between host and donor immune reactive cells plays a major role in graft-versus-leukemia (GvL) effect and graft-versus-host disease (GvHD). Immune reconstitution of the T-cell repertoire has major implications for relapsed disease, GvHD, and post-transplant viral infections. This chapter will focus on the exciting development in cellular therapy in the context of HCT and cell therapy including discussion of the diverse repertoire of T-cell products, specifically donor lymphocyte infusion (DLI), regulatory T cells, cytotoxic T lymphocytes for viral infections, and T-cell receptor gene-modified T cells. In addition, the underlying pathophysiology and mechanism of action of cell-mediated effects with a focus on evidence from clinical studies elaborating the indications, efficacy ,and safety of these T-cell-mediated therapies will be discussed, along with a brief overview of future directions and clinical trials exploring the potential of novel cell-mediated therapies in post-transplant settings.

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Further Readings

    Donor Lymphocyte Infusion

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    • De Vos J, Baudoux E, Bay JO, et al. Prophylactic, preemptive and curative use of donor lymphocyte infusion in patients undergoing allogeneic stem cell transplantation: guidelines of the SFGM-TC. Bull Cancer. 2018.10.002.

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    • El-Jurdi N, Reljic T, Kumar A, et al. Efficacy of adoptive immunotherapy with donor lymphocyte infusion in relapsed lymphoid malignancies. Immunotherapy. 2013;5(5):457–66.

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    • Frey NV, Porter DL. Graft-versus-host disease after donor leukocyte infusions: presentation and management. Best Pract Res Clin Haematol. 2008;21(2):205–22.

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    • Goldsmith SR, Slade M, DiPersio JF, et al. Donor-lymphocyte infusion following haploidentical hematopoietic cell transplantation with peripheral blood stem cell grafts and PTCy. Bone Marrow Transplant. 2017;52(12):1623–8.

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    • Miller JS, Warren EH, van den Brink MR, et al. NCI first international workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the biology underlying recurrence of malignant disease following allogeneic HSCT: graft-versus-tumor/leukemia reaction. Biol Blood Marrow Transplant. 2010;16(5):565–86.

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    • Zeidan AM, Forde PM, Symons H, et al. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2014;20(3):314–8.

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    Regulatory T (Treg) Cells

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    • Whangbo JS, Kim HT, Nikiforow S, et al. Functional analysis of clinical response to low-dose IL-2 in patients with refractory chronic graft-versus-host disease. Blood Adv. 2019;3(7):984–94.

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    Cytotoxic T Lymphocytes for Viral Infections

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      Google Scholar 

    • Neuenhahn M, Albrecht J, Odendahl M, et al. Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT. Leukemia. 2017;31:2161–71.

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    T-Cell Receptors-Gene-Modified T Cells for Cancer Treatment

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    Authors and Affiliations

    1. Clinical Fellow Division of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA

      Hamza Hashmi

    2. Cleveland Clinic Lerner College of Medicine, Blood & Marrow Transplant Program, Cleveland Clinic, Cleveland, OH, USA

      Navneet Majhail

    3. Hematology/Stem Cell Transplantation and Cellular Therapy Programs, Hematopoietic Stem Cell Apheresis Collection Facility, Cancer Treatment Centers of America, Rosalind Franklin University of Medicine and Science, Zion, IL, USA

      Syed A. Abutalib

    4. Gary Jobson Professor in Medical Oncology, Blood and Marrow Transplantation Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA

      Aaron P. Rapoport

    5. Blood and Marrow Transplantation and Cellular Therapy Program, BMT/CT Education Program, University of Maryland School of Medicine, Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA

      Jean A. Yared

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    1. Hamza Hashmi
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    2. Navneet Majhail
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    3. Syed A. Abutalib
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    4. Aaron P. Rapoport
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    Editors and Affiliations

    1. Center for Hematologic Malignancies Adult Blood and Marrow Transplant & Cell Therapy Program, Knight Cancer Institute Oregon Health & Science University, Portland, OR, USA

      Richard T. Maziarz

    2. Center for Hematologic Malignancies Adult Blood and Marrow Transplant & Cell Therapy Program, Knight Cancer Institute Oregon Health & Science University, Portland, OR, USA

      Susan Schubach Slater

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    Hashmi, H., Majhail, N., Abutalib, S.A., Rapoport, A.P., Yared, J.A. (2021). T-Cell Therapeutics: Donor Lymphocyte Infusion, Cytotoxic T-Lymphocyte Infusion, and Other Non-CAR T-Cell Therapies. In: Maziarz, R.T., Slater, S.S. (eds) Blood and Marrow Transplant Handbook. Springer, Cham. https://doi.org/10.1007/978-3-030-53626-8_55

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