Exercise as an Immune Adjuvant for Allogeneic Cell Therapies

Summary

This study aims to improve the treatment of blood cancer by using exercise to collect healthier immune cells from donors. Allogeneic adoptive cell therapy is a treatment where immune cells from a healthy donor are given to a cancer patient, usually to help prevent or treat cancer relapse after a stem cell transplant. These donor cells can either be directly infused into the patient or grown in a lab to create more specialized immune cells that target and kill cancer. While this therapy has been helpful for many patients, there is a need to make it more effective for a larger group and reduce side effects like graft-versus-host disease (GvHD), where the donor's immune cells attack the patient's healthy tissue. This Early Phase 1 trial will test whether exercise can help produce better immune cells from donors. The investigators will recruit healthy participants for three study groups: 1. Exercise Group: Participants will complete a 20-minute cycling exercise session. The investigators will collect blood samples before, during, and after exercise to study the number and quality of immune cells. The investigators will also use the collected cells to create immune therapies and test their ability to kill cancer cells in the lab and control cancer growth in mice. 2. Exercise and Beta Blocker Group: In this group, participants will complete up to five cycling sessions, with at least a week between each session. Before each session, participants will take either a placebo or a drug (beta blocker) that blocks stress hormones like adrenaline. The investigators will collect blood samples before and during exercise to see how blocking these hormones changes the effect of exercise on immune cells. 3. Isoproterenol Group: Participants in this group will receive a 20-minute infusion of isoproterenol, a drug that mimics the effects of adrenaline. The investigators will collect blood samples before, during, and after the infusion to see if the drug causes similar immune changes to those caused by exercise. Participants can join one, two, or all three groups. This research will help understand whether exercise can improve immune cell therapies for treating blood cancer and reduce the risk of GvHD, making these treatments safer and more effective.

Timeline

Start

2018-01-24

Primary completion

2031-05-31

Completion

2031-05-31

Publications

• Background Filioglou D, Leite GSF, Batatinha H, Santa-Cruz N, Davini DW, Baker FL, Simpson RJ, Katsanis E. Cytokine-induced memory-like NK cells combined with Tafasitamab demonstrate efficacy against B-cell acute lymphoblastic leukemia. Immunother Adv. 2025 Jul 16;5(1):ltaf025. doi: 10.1093/immadv/ltaf025. eCollection 2025.
• Results Baker FL, Smith KA, Mylabathula PL, Zuniga TM, Diak DM, Batatinha H, Niemiro GM, Seckeler MD, Pedlar CR, O'Connor DP, Colombo J, Katsanis E, Simpson RJ. Exercise-induced beta2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded gammadelta T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition. Cancer Res Commun. 2024 May 13;4(5):1253-1267. doi: 10.1158/2767-9764.CRC-23-0570.
• Results Smith KA, Batatinha H, Niemiro GM, Baker FL, Zuniga TM, Diak DM, Mylabathula PL, Kistner TM, Davini D, Hoffman E, Colombo JN, Seckeler MD, Bond RA, Katsanis E, Simpson RJ. Exercise-induced beta2-adrenergic receptor activation enhances effector lymphocyte mobilization in humans and suppresses lymphoma growth in mice through NK-cells. Brain Behav Immun. 2025 Aug;128:751-765. doi: 10.1016/j.bbi.2025.04.040. Epub 2025 Apr 29.
• Results McDougal LM, Baker FL, Gustafson MP, Katsanis E, Simpson RJ. Exercise-mobilized donor lymphocyte infusions enhanced with cytokine stimulation for the prevention and treatment of leukemic relapse after allogeneic hematopoietic cell transplantation. Front Immunol. 2025 Jun 12;16:1563972. doi: 10.3389/fimmu.2025.1563972. eCollection 2025.
• Results Batatinha H, Pena NA, Hoskin GA, Kistner TM, Diak DM, Niemiro GM, Katsanis E, Simpson RJ. Exercise Delays Human Leukemia Progression and Mitigates Graft-Versus-Host Disease After Donor Lymphocyte Infusion in Xenogeneic Mice. Cancers (Basel). 2025 Aug 29;17(17):2826. doi: 10.3390/cancers17172826.
• Results Batatinha H, Niemiro GM, Pena NA, Hoskin GA, Zuniga TM, Smith KA, Baker FL, Diak DM, Mylabathula PL, Kistner TM, Seckeler MD, Katsanis E, Simpson RJ. Isoproterenol infusion enhances composition and function of G-CSF mobilized allogeneic peripheral blood hematopoietic cell grafts. Stem Cell Res Ther. 2025 Nov 5;16(1):614. doi: 10.1186/s13287-025-04725-4.
• Results Batatinha H, Valenzuela AM, Filioglou D, Wilde P, Leite G, Kistner TM, Baker FL, Katsanis E, Simpson RJ. Exercise-mobilized lymphocytes enhance the function of cytokine-induced memory-like NK cells against myeloid leukemia. Blood Adv. 2026 Apr 14;10(7):2565-2577. doi: 10.1182/bloodadvances.2025018345.
• Results Zuniga TM, Baker FL, Smith KA, Batatinha H, Lau B, Gustafson MP, Katsanis E, Simpson RJ. Acute exercise mobilizes NKT-like cells with a cytotoxic transcriptomic profile but does not augment the potency of cytokine-induced killer (CIK) cells. Front Immunol. 2022 Sep 14;13:938106. doi: 10.3389/fimmu.2022.938106. eCollection 2022.
• Results Zuniga TM, Baker FL, Smith KA, Batatinha H, Lau B, Burgess SC, Gustafson MP, Katsanis E, Simpson RJ. Clonal Kinetics and Single-Cell Transcriptional Profiles of T Cells Mobilized to Blood by Acute Exercise. Med Sci Sports Exerc. 2023 Jun 1;55(6):991-1002. doi: 10.1249/MSS.0000000000003130. Epub 2023 Jan 26.
• Results Batatinha H, Diak DM, Niemiro GM, Baker FL, Smith KA, Zuniga TM, Mylabathula PL, Seckeler MD, Lau B, LaVoy EC, Gustafson MP, Katsanis E, Simpson RJ. Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice. Front Immunol. 2023 Apr 3;14:1067369. doi: 10.3389/fimmu.2023.1067369. eCollection 2023.
• Chou L, Valenzuela AM, McDougal LM, Baker FL, Katsanis E, Simpson RJ. Exercise-mobilized lymphocytes enhance antibody-based immunotherapy in multiple myeloma through CD16+ NK cell-mediated cytotoxicity. J Transl Med. 2026 Mar 3;24(1):483. doi: 10.1186/s12967-026-07888-7.

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