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Specific Adoptive T-Cell Therapy for Viral and Fungal Infections

  • Lawrence G. Lum
  • Catherine M. Bollard
Chapter

Abstract

Despite advances in anti-infective agents, viral and fungal infections after hematopoietic stem cell transplantation (HSCT) continue to cause life-threatening complications that limit the success of HSCT. Early adoptive T-cell immunotherapy studies showed that administration of allogeneic virus-specific cytotoxic T lymphocytes (vCTL) can prevent and control viral infections and reconstitute antiviral immunity to cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Advances in immunobiology, in vitro culture technology, and current good manufacturing practice (cGMP) have provided opportunities for advancing adoptive cell therapy for viral infections: (1) T cells have been expanded targeting multiple pathogens; (2) vCTL production no longer requires viral infection or viral vector transduction of antigen-presenting cells (APCs); (3) the source of lymphocytes is no longer restricted to donors who are immune to the pathogens; (4) naive T cells have been redirected with chimeric antigen receptor T cells (CARTs) or armed with bispecific antibody-armed T cells (BATs) to mediate vCTL activity; (5) these technologies could be combined to targeted multiple viral or fungal pathogens; and (6) pathogen-specific T-cell products manufactured from third parties and banked for “off-the-shelf” use post-HSCT may soon become a reality.

Keywords

Adoptive immunotherapy Stem cell transplantation Virus-specific cytotoxic T cells Bispecific antibody-armed T cells Chimeric antigen receptor T cells Viral infections 

Notes

Acknowledgments

Special thanks to the clinical coordinators for dedicating their efforts to serve the immunotherapy patients. We thank Manley Huang for his thoughtful reading of the chapter. The studies were supported in part by R01 CA140314 (LGL) and R01 CA182526 (LGL), Translational Grants #6092-09 (LGL) and #6066-06 (LGL) from the Leukemia & Lymphoma Society, and UVA Cancer Center Support Grant NCI 5P30CA044579-24. LGL is a founder of Transtarget, Inc. CMB is supported in part by the NICHD K12-HD-001399 award to MDK and CPRIT R01 RP100469 and NCI P01 CA148600-02 awards to CMB.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cellular Therapy and Stem Cell Transplant Program, Emily Couric Cancer CenterUniversity of VirginiaCharlottesvilleUSA
  2. 2.Program for Cell Enhancement and Technologies for Immunotherapy, Sheikh Zayed Institute for Pediatric Surgical Innovation, and Center for Cancer and Immunology Research, Children’s National Health SystemWashington, DCUSA

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