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Cited by 37Hematopoietic Stem Cell TransplantationT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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Minor Histocompatibility Antigen-Specific T Cells

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Summers, Corinne, Sheth, Vipul S., Bleakley, Marie·2020·Frontiers in Pediatrics
DOI 10.3389/fped.2020.00284PMC PMC7283489
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Abstract

Minor Histocompatibility (H) antigens are major histocompatibility complex (MHC)/Human Leukocyte Antigen (HLA)-bound peptides that differ between allogeneic hematopoietic stem cell transplantation (HCT) recipients and their donors as a result of genetic polymorphisms. Some minor H antigens can be used as therapeutic T cell targets to augment the graft-vs.-leukemia (GVL) effect in order to prevent or manage leukemia relapse after HCT. Graft engineering and post-HCT immunotherapies are being developed to optimize delivery of T cells specific for selected minor H antigens. These strategies have the potential to reduce relapse risk and thereby permit implementation of HCT approaches that are associated with less toxicity and fewer late effects, which is particularly important in the growing and developing pediatric patient. Most minor H antigens are expressed ubiquitously, including on epithelial tissues, and can be recognized by donor T cells following HCT, leading to graft-vs.-host disease (GVHD) as well as GVL. However, those minor H antigens that are expressed predominantly on hematopoietic cells can be targeted for selective GVL. Once full donor hematopoietic chimerism is achieved after HCT, hematopoietic-restricted minor H antigens are present only on residual recipient malignant hematopoietic cells, and these minor H antigens serve as tumor-specific antigens for donor T cells. Minor H antigen-specific T cells that are delivered as part of the donor hematopoietic stem cell graft at the time of HCT contribute to relapse prevention. However, in some cases the minor H antigen-specific T cells delivered with the graft may be quantitatively insufficient or become functionally impaired over time, leading to leukemia relapse. Following HCT, adoptive T cell immunotherapy can be used to treat or prevent relapse by delivering large numbers of donor T cells targeting hematopoietic-restricted minor H antigens. In this review, we discuss minor H antigens as T cell targets for augmenting the GVL effect in engineered HCT grafts and for post-HCT immunotherapy. We will highlight the importance of these developments for pediatric HCT.

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Metadata

Authors
Summers, C., Sheth, V. S., & Bleakley, M.
Affiliations
  • University of Washington (US)
  • Fred Hutch Cancer Center (US)
Corresponding author
Bleakley, Marie
ORCID
Venue
Frontiers in Pediatrics
Publisher
Frontiers Media SA
Published
2020-06-03
Volume
8
Pages
284-284
ISSN
2296-2360 (ISSN-L)
DOI
10.3389/fped.2020.00284
PMC
PMC7283489
OpenAlex
W3033247189
Cited by
37
References
1
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 4 · 2020: 1
FWCI
0.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pediatrics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Association for Cancer Research (SU2C-AACR-IRG 14-17)
  • Alex's Lemonade Stand Foundation for Childhood Cancer
  • Stand Up To Cancer
  • National Cancer Institute (CA018029, P01CA018029)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
minor histocompatibility antigens, graft-versus-leukemia effect, graft-versus-host disease, hematopoietic stem cell transplantation, leukemia relapse, adoptive T cell therapy, graft engineering, hematopoietic chimerism, pediatric hematopoietic stem cell transplantation, MHC-bound peptides

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