Faculty Collaboration Database

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 2003 Jul;32(2):177-86

Date

07/03/2003

Pubmed ID

12838283

DOI

10.1038/sj.bmt.1704086

Scopus ID

2-s2.0-10744220588 (requires institutional sign-in at Scopus site)   216 Citations

Abstract

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-gamma, TNF-alpha and IL1-beta, with increases in IL-6 and IFN-gamma 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 x 10(6) IU/m(2)/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.

Author List

Burns LJ, Weisdorf DJ, DeFor TE, Vesole DH, Repka TL, Blazar BR, Burger SR, Panoskaltsis-Mortari A, Keever-Taylor CA, Zhang MJ, Miller JS

Author

Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Breast Neoplasms
Cytokines
Female
Hematopoietic Stem Cell Transplantation
Humans
Immunity, Cellular
Immunotherapy
Interleukin-2
Killer Cells, Natural
Lymphocyte Transfusion
Lymphoma
Male
Matched-Pair Analysis
Middle Aged
Transplantation, Autologous