Abstract
Haematology has been at the forefront of cancer immunotherapy advancements. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is one of the earliest forms of cancer immunotherapy and continues to cure thousands of patients. Donor lymphocyte infusion (DLI) increases allo-HSCT efficacy and reduces graft-versus-host disease (GVHD). In recent years, chimeric antigen receptor (CAR)-T-cells have been approved for the treatment of distinct haematologic malignancies, producing durable response in otherwise untreatable patients. New target antigen identification and technological advances have enabled the structural and functional evolution of CARs, broadening their applications. Despite successes, adoptive T-cell (ATC) therapies are expensive, can cause severe adverse reactions and their use is restricted to few patients. This review considers the current status and future perspectives of allogeneic transplant and donor lymphocytes, as well as novel ATC therapies, such as CAR-T-cells in haematological malignancies by analysing their strengths, weaknesses, opportunities, and threats (SWOT). The biological rationale for anti-cancer mechanisms and development; current clinical data in specific haematological malignancies; efficacy, toxicity, response and resistance profiles; novel strategies to improve these characteristics; and potential targets to enhance or expand the application of these therapies are discussed.
Highlights
Haematology boasts the first clinical application of one of the oldest forms of cancer immunotherapy: allogeneic hematopoietic stem cell transplantation
In 1990, Kolb et al showed that Donor lymphocyte infusion (DLI) could achieve disease remission following relapse after nonmyeloablative allogeneic transplant for chronic myelogenous leukaemia (CML) [15]
According to the Centre for International Blood and Marrow Transplant Research (CIBMTR) [21], the number of allo-Haematopoietic Stem Cell Transplant (HSCT) in the USA increased by 1% in 2018, whereas autologous HSCTs decreased by 5%
Summary
ATC therapies demonstrate outstanding therapeutic potential in haematological malignancies. Considering their strengths, weaknesses, opportunities and threats is essential to directing future investigation of their therapeutic potential (Table I). Allo-HSCT and DLI are widely used immunotherapies that continue to cure many patients with haematological malignancies. Allo-HSCT and novel strategies for DLI modifications are still widely investigated. Novel ATC therapies have produced remarkable responses in patients. They involve costly development of a new therapeutic agent that is unique for each patient, while T-cells take weeks to culture and patients require considerable hospitalisation to receive treatment [134]. MHC restriction and the specificity of genomic aberrations to the cancer being targeted prevent individual-synthesised ATC therapies from being expanded across the general population, unlike agents such as immune checkpoint inhibitors and bispecific T-cell engagers which are broad-based, cost-effective, off-the-shelf agents
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
