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Immunotherapy

IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial

Bone Marrow Transplantation volume 32, pages 177–186 (2003)Cite this article

Summary:

We determined the safety, immune activating effects, and potential efficacy of i.v. infusion of ex vivo interleukin-2 (IL-2) activated natural killer (NK) cells (part I) or IL-2 boluses (part II) during daily s.c. IL-2 administration following hematopoietic recovery from autologous transplantation. In all, 57 patients with relapsed lymphoma (n=29) or metastatic breast cancer (n=28) were enrolled. In part I of the study, 34 patients were enrolled at three dose levels of ex vivo IL-2-activated NK cells. Lymphaphereses were performed on days 28 and 42 of s.c. IL-2 administration. Following overnight ex vivo IL-2 activation of the pheresis product, the cells were reinfused the following day. In part II, 23 patients were enrolled at three dose levels of supplemental i.v. IL-2 bolus infusions, given on days 28 and 35 during s.c. IL-2 administration. Toxicities were generally mild, and no patient required hospitalization. Lytic function was markedly enhanced for fresh peripheral blood mononuclear cells (PBMNCs) obtained 1 day postinfusion of either IL-2-activated cells or IL-2 boluses. IL-2 boluses transiently increased the levels of IL-6, IFN-γ, TNF-α and IL1-β, with increases in IL-6 and IFN-γ being dose dependent. A total of 37 patients (19 patients with lymphoma, 18 with breast cancer) treated with an optimum dose of post-transplant immunotherapy (defined as having received 1.75 × 106 IU/m2/day of s.c. IL-2 plus at least one of the planned ex vivo IL-2-activated cell infusions/IL-2 boluses) could be matched with controls from the Autologous Blood and Marrow Transplant Registry database. The matched-pairs analysis demonstrated no improvement in disease outcomes of survival and relapse. We conclude that IL-2-activated cells/IL-2 boluses can be safely administered, generate PBMNCs with enhanced cytotoxicity against NK-resistant targets, and increase cytokine levels. With this dose and schedule of administration of IL-2, no improvement in patient disease outcomes was noted. Alternative strategies will be needed to exploit the immunotherapeutic potential of IL-2-activated NK cells.

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Acknowledgements

We thank RN Juliette Gay and RN Cindy Steele for providing assistance in patient care, RN Roby Nicklow, RN Eva Gallagher, Victoria Johnson, and Melissa Walker for data management, MD Fred Sanchez for patient care, and Maurice Wolin and Priscilla Ayers (Chiron). LJB is the recipient of a Department of Defense grant, and is also supported by the Janie Lymphoma Research Fund and the Minnesota Medical Foundation. This work was supported in part by National Institute of Health Grant PO1-CA-65493 (JSM), R21CA78904 (DJW) and Grant M01-RR00400 from the National Center for Research Resources. We also acknowledge the support of the Bone Marrow Transplant Research Fund of the University of Minnesota and the Masonic Order of the Eastern Star.

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Authors and Affiliations

  1. Blood and Marrow Transplant Program and Cancer Center, Minneapolis, MN, USA

    L J Burns, D J Weisdorf, T E DeFor, T L Repka, B R Blazar, A Panoskaltsis-Mortari & J S Miller

  2. Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    S R Burger

  3. Medical College of Wisconsin, Milwaukee, WI, USA

    D H Vesole, C A Keever-Taylor & M-J Zhang

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Burns, L., Weisdorf, D., DeFor, T. et al. IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial. Bone Marrow Transplant 32, 177–186 (2003). https://doi.org/10.1038/sj.bmt.1704086

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