A single bout of dynamic exercise enhances the expansion of MAGE-A4 and PRAME-specific cytotoxic T-cells from healthy adults

Emily C P LaVoy; Catherine M Bollard; Patrick J Hanley; James W Blaney; Daniel P O'Connor; Jos A Bosch; Richard J Simpson

A single bout of dynamic exercise enhances the expansion of MAGE-A4 and PRAME-specific cytotoxic T-cells from healthy adults

Exerc Immunol Rev. 2015:21:144-53.

Authors

Emily C P LaVoy¹, Catherine M Bollard², Patrick J Hanley², James W Blaney³, Daniel P O'Connor¹, Jos A Bosch^{1

4}, Richard J Simpson¹

Affiliations

¹ Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX, USA.
² Program for Cell Enhancement and Technologies for Immunotherapy, Children's National Health System and The George Washington University, Washington D.C., USA.
³ Baylor College of Medicine, Texas Children's Hospital, Center for Cell and Gene Therapy, Houston, TX, USA.
⁴ Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands.

PMID: 25826370

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.

Keywords: CTLs; Immunotherapy; Vienna Active Ageing Study.; adoptive transfer; physical activity; tumor-associated-antigens.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Antigen Presentation
Antigens, Neoplasm / immunology*
Cells, Cultured
Cytotoxicity, Immunologic
Dendritic Cells / immunology
Exercise Test
Exercise*
Female
Healthy Volunteers
Hematopoietic Stem Cell Transplantation
Hormones / blood
Humans
Immunotherapy, Adoptive
Leukocyte Count
Male
Neoplasm Proteins / immunology*
T-Cell Antigen Receptor Specificity
T-Lymphocytes, Cytotoxic / immunology*
Transplantation, Autologous
WT1 Proteins / immunology

Substances

Antigens, Neoplasm
Hormones
MAGEA4 protein, human
Neoplasm Proteins
PRAME protein, human
WT1 Proteins
WT1 protein, human