| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Recent studies have indicated that adoptive immunotherapy with autologous antitumor tumor-infiltrating lymphocytes (TILs) following nonmyeloablative chemotherapy mediates tumor regression in 
50% of treated patients with metastatic melanoma, and that tumor regression is correlated with the degree of persistence of adoptively transferred T cells in peripheral blood. These findings, which suggested that the proliferative potential of transferred T cells may play a role in clinical responses, led to the current studies in which telomere length as well as phenotypic markers expressed on the administered TILs were examined. TILs that were associated with objective clinical responses following adoptive transfer possessed a mean telomere length of 6.3 kb, whereas TILs that were not associated with significant clinical responses were significantly shorter, averaging 4.9 kb (p < 0.01). Furthermore, individual TIL-derived T cell clonotypes that persisted in vivo following adoptive cell transfer possessed telomeres that were longer than telomeres of T cell clonotypes that failed to persist (6.2 vs 4.5 kb, respectively; p < 0.001). Expression of the costimulatory molecule CD28 also appeared to be associated with long telomeres and T cell persistence. These results, indicating that the telomere length of transferred lymphocytes correlated with in vivo T cell persistence following adoptive transfer, and coupled with the previous observation that T cell persistence was associated with clinical responses in this adoptive immunotherapy trial, suggest that telomere length and the proliferative potential of the transferred T cells may play a significant role in mediating response to adoptive immunotherapy.
This article has been cited by other articles:
|
|
 |
|
  C. A. Klebanoff, Z. Yu, L. N. Hwang, D. C. Palmer, L. Gattinoni, and N. P. Restifo Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination Blood, August 27, 2009; 114(9): 1776 - 1783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Carpenito, M. C. Milone, R. Hassan, J. C. Simonet, M. Lakhal, M. M. Suhoski, A. Varela-Rohena, K. M. Haines, D. F. Heitjan, S. M. Albelda, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains PNAS, March 3, 2009; 106(9): 3360 - 3365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Casado, O. DelaRosa, G. Pawelec, E. Peralbo, E. Duran, F. Barahona, R. Solana, and R. Tarazona Correlation of effector function with phenotype and cell division after in vitro differentiation of naive MART-1-specific CD8+ T cells Int. Immunol., January 1, 2009; 21(1): 53 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Dudley and S. A. Rosenberg Clinical Trials Investigating Adoptive Cell Therapy Combined with Lymphodepletion for Patients with Advanced Cancer ASCO Educational Book, January 1, 2009; 2009(1): 516 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Boni, P. Muranski, L. Cassard, C. Wrzesinski, C. M. Paulos, D. C. Palmer, L. Gattinoni, C. S. Hinrichs, C.-C. Chan, S. A. Rosenberg, et al. Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriers Blood, December 1, 2008; 112(12): 4746 - 4754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Dudley, J. C. Yang, R. Sherry, M. S. Hughes, R. Royal, U. Kammula, P. F. Robbins, J. Huang, D. E. Citrin, S. F. Leitman, et al. Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens J. Clin. Oncol., November 10, 2008; 26(32): 5233 - 5239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zappasodi, M. Di Nicola, C. Carlo-Stella, R. Mortarini, A. Molla, C. Vegetti, S. Albani, A. Anichini, and A. M. Gianni The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells Haematologica, October 1, 2008; 93(10): 1523 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Tatum, L. M. Mylin, S. J. Bender, M. A. Fischer, B. A. Vigliotti, M. J. Tevethia, S. S. Tevethia, and T. D. Schell CD8+ T Cells Targeting a Single Immunodominant Epitope are Sufficient for Elimination of Established SV40 T Antigen-Induced Brain Tumors J. Immunol., September 15, 2008; 181(6): 4406 - 4417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Newrzela, K. Cornils, Z. Li, C. Baum, M. H. Brugman, M. Hartmann, J. Meyer, S. Hartmann, M.-L. Hansmann, B. Fehse, et al. Resistance of mature T cells to oncogene transformation Blood, September 15, 2008; 112(6): 2278 - 2286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Darcy IL-21 priming enhances T-cell immunotherapy Blood, June 1, 2008; 111(11): 5268 - 5269. [Full Text] [PDF]
|
|
|
|
|
|
C. S. Hinrichs, R. Spolski, C. M. Paulos, L. Gattinoni, K. W. Kerstann, D. C. Palmer, C. A. Klebanoff, S. A. Rosenberg, W. J. Leonard, and N. P. Restifo IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy Blood, June 1, 2008; 111(11): 5326 - 5333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Coccoris, E. Swart, M. A. de Witte, J. W. J. van Heijst, J. B. A. G. Haanen, K. Schepers, and T. N. M. Schumacher Long-Term Functionality of TCR-Transduced T Cells In Vivo J. Immunol., May 15, 2008; 180(10): 6536 - 6543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Montes, A. I. Chapoval, J. Nelson, V. Orhue, X. Zhang, D. H. Schulze, S. E. Strome, and B. R. Gastman Tumor-Induced Senescent T Cells with Suppressor Function: A Potential Form of Tumor Immune Evasion Cancer Res., February 1, 2008; 68(3): 870 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barber, T. Zhang, and C. L. Sentman Immunotherapy with Chimeric NKG2D Receptors Leads to Long-Term Tumor-Free Survival and Development of Host Antitumor Immunity in Murine Ovarian Cancer J. Immunol., January 1, 2008; 180(1): 72 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yang, E. M. Wall, K. Milne, P. Theiss, P. Watson, and B. H. Nelson CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15 Dependent Mechanism Clin. Cancer Res., December 1, 2007; 13(23): 7172 - 7180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hsu, S. A. Jones, C. J. Cohen, Z. Zheng, K. Kerstann, J. Zhou, P. F. Robbins, P. D. Peng, X. Shen, T. J. Gomes, et al. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene Blood, June 15, 2007; 109(12): 5168 - 5177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Butler, J.-S. Lee, S. Ansen, D. Neuberg, F. S. Hodi, A. P. Murray, L. Drury, A. Berezovskaya, R. C. Mulligan, L. M. Nadler, et al. Long-Lived Antitumor CD8+ Lymphocytes for Adoptive Therapy Generated Using an Artificial Antigen-Presenting Cell Clin. Cancer Res., March 15, 2007; 13(6): 1857 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mackensen, N. Meidenbauer, S. Vogl, M. Laumer, J. Berger, and R. Andreesen Phase I Study of Adoptive T-Cell Therapy Using Antigen-Specific CD8+ T Cells for the Treatment of Patients With Metastatic Melanoma J. Clin. Oncol., November 1, 2006; 24(31): 5060 - 5069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Markel, R. Seidman, N. Stern, T. Cohen-Sinai, O. Izhaki, G. Katz, M. Besser, A. J. Treves, R. S. Blumberg, R. Loewenthal, et al. Inhibition of Human Tumor-Infiltrating Lymphocyte Effector Functions by the Homophilic Carcinoembryonic Cell Adhesion Molecule 1 Interactions J. Immunol., November 1, 2006; 177(9): 6062 - 6071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Johnson, B. Heemskerk, D. J. Powell Jr., C. J. Cohen, R. A. Morgan, M. E. Dudley, P. F. Robbins, and S. A. Rosenberg Gene Transfer of Tumor-Reactive TCR Confers Both High Avidity and Tumor Reactivity to Nonreactive Peripheral Blood Mononuclear Cells and Tumor-Infiltrating Lymphocytes J. Immunol., November 1, 2006; 177(9): 6548 - 6559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sensi and A. Anichini Unique Tumor Antigens: Evidence for Immune Control of Genome Integrity and Immunogenic Targets for T Cell-Mediated Patient-Specific Immunotherapy Clin. Cancer Res., September 1, 2006; 12(17): 5023 - 5032. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
