title: A single bout of dynamic exercise enhances the expansion of MAGE-A4 and PRAME-specific cytotoxic T-cells from healthy adults.
abstract: The ex vivo expansion of tumor-associated-antigen (TAA)- specific cytotoxic T-cells (CTLs) from healthy donors for adoptive transfer to cancer patients is now providing additional treatment options for patients. Many studies have shown that adoptive transfer of expanded CTLs can reduce the risk of relapse in cancer patients following hematopoietic stem cell transplantation (HSCT). However, the procedure can be limited by difficulties in priming and expanding sufficient numbers of TAA-specific-CTLs. Because acute dynamic exercise mobilizes large numbers of T-cells to peripheral blood, we hypothesized that a single bout of exercise would augment the ex vivo expansion of TAA-specific-CTLs.We therefore collected lymphocytes from blood donated by healthy adults at rest and after brief maximal dynamic exercise. TAA-specific CTLs were expanded using autologous monocyte-derived-dendritic cells pulsed with melanoma-associated antigen 4 (MAGE-A4), with preferentially expressed antigen in melanoma (PRAME), and with Wilms' tumor protein (WT-1). Post exercise, 84% of the participants had a greater number of CTLs specific for at least one of the three TAA.Cells expanded from post exercise blood yielded a greater number of MAGE-A4 and PRAME-specific-cells in 70% and 61% of participants, respectively. In the 'exercise-responsive' participants (defined as participants with at least a 10% increase in TAA-specific-CTLs post-exercise), MAGEA4- and PRAME-specific-CTLs increased 3.4-fold and 6.2- fold respectively. Moreover, expanded TAA-specific CTLs retained their antigen-specific cytotoxic activity. No phenotype differences were observed between expanded cells donated at rest and postexercise. We conclude that exercise can enhance the ex vivo expansion of TAA-specific-CTLs from healthy adults without compromising cytotoxic function. Hence, this study has implications for immunotherapy using adoptive T-cell transfer of donor-derived T-cells after allogeneic HSCT.
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA.
authors.forename: Emily C P
authors.initials: EC
authors.lastname: LaVoy
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington D.C., USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington D.C., USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.affiliation: Baylor College of Medicine, Texas Children's Hospital, Center for Cell and Gene Therapy, Houston, TX, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Blaney
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: O'Connor
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA.|Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jos A
authors.initials: JA
authors.lastname: Bosch
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simpson
mesh_terms: D000328:Adult; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D015444:Exercise; D005080:Exercise Test; D005260:Female; D064368:Healthy Volunteers; D018380:Hematopoietic Stem Cell Transplantation; D006728:Hormones / Q000097:blood; D006801:Humans; D016219:Immunotherapy, Adoptive; D007958:Leukocyte Count; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014182:Transplantation, Autologous; D025721:WT1 Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D006728:Hormones; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; C404944:PRAME protein, human; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: CTLs; Immunotherapy; Vienna Active Ageing Study.; adoptive transfer; physical activity; tumor-associated-antigens