| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
Department of 1 Molecular Virology, Immunology, and Medical Genetics, 2 Medical Scientist Program, Department of Pathology, 3 Division of Cancer Immunology, Department of Internal Medicine, 4 Division of Hematology/Oncology, 5 Division of Epidemiology and Biometrics, 6 The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
Adoptive immunotherapy with tumor-specific T cells has emerged as a valid approach for prevention or treatment of diseases, such as melanoma and EBV-associated lymphoma. As interleukin (IL) 15 promotes survival of CD8+ memory CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo through the maintenance of adoptively transferred memory CTL. To test this, we treated mice bearing P1A+ tumors with adoptively transferred T cells possessing a transgenic V
8+ T-cell receptor specific for the P1A tumor antigen (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5 µg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a significantly delayed tumor relapse or complete tumor regression (P < 0.002 compared with PBS), with a striking persistence of the CD8+ V8+ P1CTL compared with mice receiving the CD8+ V8+ P1CTL and PBS vehicle (26.3 versus 5.1% P < 10–5). Animals exhibiting complete tumor regression had a significant population of CD8+ V8+ P1CTL (46%) that persisted with IL-15 treatment until 140 days after adoptive transfer and successfully defended them against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection over vehicle and resulted in lower percentages of T cells with an activated memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor cytotoxicity compared with mice treated with IL-15. Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy.
This article has been cited by other articles:
|
|
 |
|
  T. Iuchi, S. Teitz-Tennenbaum, J. Huang, B. G. Redman, S. D. Hughes, M. Li, G. Jiang, A. E. Chang, and Q. Li Interleukin-21 Augments the Efficacy of T-Cell Therapy by Eliciting Concurrent Cellular and Humoral Responses Cancer Res., June 1, 2008; 68(11): 4431 - 4441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fujita, X. Zhu, K. Sasaki, R. Ueda, K. L. Low, I. F. Pollack, and H. Okada Inhibition of STAT3 Promotes the Efficacy of Adoptive Transfer Therapy Using Type-1 CTLs by Modulation of the Immunological Microenvironment in a Murine Intracranial Glioma J. Immunol., February 15, 2008; 180(4): 2089 - 2098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-R. Kim, K.-A Hwang, and I. Kang Dual Roles of IL-15 in Maintaining IL-7R{alpha}lowCCR7 Memory CD8+ T Cells in Humans via Recovering the Phosphatidylinositol 3-Kinase/AKT Pathway J. Immunol., November 15, 2007; 179(10): 6734 - 6740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Wall, K. Milne, M. L. Martin, P. H. Watson, P. Theiss, and B. H. Nelson Spontaneous Mammary Tumors Differ Widely in Their Inherent Sensitivity to Adoptively Transferred T Cells Cancer Res., July 1, 2007; 67(13): 6442 - 6450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. May Jr, K. Lute, E. Kocak, S. Abdessalam, L. Yin, O. Li, Z. Guan, G. Philips, P. Zheng, and Y. Liu Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice Blood, January 1, 2007; 109(1): 253 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Stoklasek, K. S. Schluns, and L. Lefrancois Combined IL-15/IL-15R{alpha} Immunotherapy Maximizes IL-15 Activity In Vivo J. Immunol., November 1, 2006; 177(9): 6072 - 6080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Blaser, N. R. Schwind, S. Karol, D. Chang, S. Shin, S. Roychowdhury, B. Becknell, A. K. Ferketich, D. F. Kusewitt, B. R. Blazar, et al. Trans-presentation of donor-derived interleukin 15 is necessary for the rapid onset of acute graft-versus-host disease but not for graft-versus-tumor activity Blood, October 1, 2006; 108(7): 2463 - 2469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Cornish, L. V. Sinclair, and D. A. Cantrell Differential regulation of T-cell growth by IL-2 and IL-15 Blood, July 15, 2006; 108(2): 600 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Nishimura, J. E. Dusak, J. Eguchi, X. Zhu, A. Gambotto, W. J. Storkus, and H. Okada Adoptive Transfer of Type 1 CTL Mediates Effective Anti-Central Nervous System Tumor Response: Critical Roles of IFN-Inducible Protein-10. Cancer Res., April 15, 2006; 66(8): 4478 - 4487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Frey and N. Monu Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response J. Leukoc. Biol., April 1, 2006; 79(4): 652 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hsu, M. S. Hughes, Z. Zheng, R. B. Bray, S. A. Rosenberg, and R. A. Morgan Primary Human T Lymphocytes Engineered with a Codon-Optimized IL-15 Gene Resist Cytokine Withdrawal-Induced Apoptosis and Persist Long-Term in the Absence of Exogenous Cytokine J. Immunol., December 1, 2005; 175(11): 7226 - 7234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Blaser, S. Roychowdhury, D. J. Kim, N. R. Schwind, D. Bhatt, W. Yuan, D. F. Kusewitt, A. K. Ferketich, M. A. Caligiuri, and M. Guimond Donor-derived IL-15 is critical for acute allogeneic graft-versus-host disease Blood, January 15, 2005; 105(2): 894 - 901. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
