Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic hematopoietic stem cell transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (HCT) is currently the standard of care for most patients with high-risk acute leukemias and some other hematologic malignancies. Although HCT can be curative, many patients who undergo allogeneic HCT will later relapse. There is, therefore, a critical need for the development of novel post-HCT therapies for patients who are at high risk for disease recurrence following HCT. One potentially efficacious approach is adoptive T-cell immunotherapy, which is currently undergoing a renaissance that has been inspired by scientific insight into the key issues that impeded its previous clinical application. Translation of the next generation of adoptive T-cell therapies to the allogeneic HCT setting, using donor T cells of defined specificity and function, presents a unique set of challenges and opportunities. The challenges, progress and future of adoptive T-cell therapy following allogeneic HCT are discussed in this review.

Keywords::

• allogeneic transplantation
• central memory
• graft versus leukemia
• immunotherapy
• T cells

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the NIH.

Financial & competing interests disclosure

M Bleakley is the Damon Runyon-Richard Lumsden Foundation Clinical Investigator supported in part by the Damon Runyon Cancer Research Foundation (CI-57-11), and in part by K23CA154532-01 from the National Cancer Institute. CJ Turtle is supported by a K99/R00 NIH Pathway to Independence Award (1K99CA154608-01A1). SR Riddell is supported by NIH grants CA18029, CA114536 and CA136551. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

GVL/T: Graft-versus-leukemia/tumor; HCT: Hematopoietic stem cell transplantation; TCR: T-cell receptor; WT1: Wilm’s tumor 1.

GVHD: Graft-versus-host disease; HCT: Hematopoietic stem cell transplantation; TCR: T-cell receptor.