Display options
Cite
Díaz-Montero CM, Naga O, Zidan AA, et al. Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory. Am J Cancer Res. 2011;1(7):882-96
Díaz-Montero, C. M., Naga, O., Zidan, A. A., Salem, M. L., Pallin, M., Parmigiani, A., Walker, G., Wieder, E., Komanduri, K., Cole, D. J., Montero, A. J., & Lichtenheld, M. G. (2011). Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory. American journal of cancer research, 1(7), 882-96.
Díaz-Montero, C Marcela, et al. "Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory." American journal of cancer research vol. 1,7 (2011): 882-96.
Díaz-Montero CM, Naga O, Zidan AA, Salem ML, Pallin M, Parmigiani A, Walker G, Wieder E, Komanduri K, Cole DJ, Montero AJ, Lichtenheld MG. Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory. Am J Cancer Res. 2011 Aug 30;1(7):882-96. PMID: 21915391; PMCID: PMC3170749.
Copy Download .nbib Format: NLM
Share it on

Am J Cancer Res. 2011 Aug 30;1(7):882-96.

Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory.

American journal of cancer research

C Marcela Díaz-Montero, Osama Naga, Abdel-Aziz A Zidan, Mohamed L Salem, Maria Pallin, Anita Parmigiani, Gail Walker, Eric Wieder, Krishna Komanduri, David J Cole, Alberto J Montero, Mathias G Lichtenheld

Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, Sylvester Cancer Center, University of Miami, Miami, FL33136, USA.

PMID: 21915391 PMCID: PMC3170749

Abstract

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8(+) T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory.

Keywords: ACT; CD8; IL-12; Pmel; T cell therapy; melanoma; memory

References

  1. J Exp Med. 2005 Oct 3;202(7):907-12 - PubMed
  2. Aging Cell. 2009 Aug;8(4):439-48 - PubMed
  3. J Immunol. 2010 Jun 1;184(11):6320-6 - PubMed
  4. Blood. 2010 Jun 3;115(22):4384-92 - PubMed
  5. J Exp Med. 2008 Mar 17;205(3):625-40 - PubMed
  6. Cancer Res. 2011 Feb 1;71(3):768-78 - PubMed
  7. Cancer Immunol Immunother. 2008 Apr;57(4):563-72 - PubMed
  8. Immunity. 2007 Dec;27(6):985-97 - PubMed
  9. Nat Immunol. 2001 May;2(5):415-22 - PubMed
  10. Science. 2009 Jan 23;323(5913):505-9 - PubMed
  11. J Clin Invest. 2005 Jun;115(6):1616-26 - PubMed
  12. J Immunother. 2005 May-Jun;28(3):258-67 - PubMed
  13. Science. 2006 Sep 29;313(5795):1960-4 - PubMed
  14. J Exp Med. 2009 Jan 16;206(1):51-9 - PubMed
  15. Exp Dermatol. 2010 Feb;19(2):157-64 - PubMed
  16. Nat Rev Cancer. 2003 Sep;3(9):666-75 - PubMed
  17. Immunity. 2010 Aug 27;33(2):229-40 - PubMed
  18. Cancer Lett. 2011 Mar 28;302(2):85-90 - PubMed
  19. Blood. 2000 Mar 15;95(6):2024-30 - PubMed
  20. Science. 2009 Jan 23;323(5913):502-5 - PubMed
  21. Trends Immunol. 2005 Feb;26(2):111-7 - PubMed
  22. Curr Opin Lipidol. 2009 Apr;20(2):98-105 - PubMed
  23. J Immunol. 2006 Dec 1;177(11):7515-9 - PubMed
  24. Immunity. 2007 Aug;27(2):281-95 - PubMed
  25. Nat Clin Pract Oncol. 2006 Dec;3(12):668-81 - PubMed
  26. Nat Med. 2009 Jul;15(7):808-13 - PubMed
  27. J Immunol. 2011 Jun 15;186(12):6965-71 - PubMed
  28. Nature. 1977 Sep 29;269(5627):417-8 - PubMed
  29. J Immunother. 2010 Jan;33(1):1-7 - PubMed
  30. Immunology. 1988 Sep;65(1):87-92 - PubMed
  31. J Dermatol Sci. 2005 Aug;39(2):105-12 - PubMed
  32. Blood. 2011 Jan 20;117(3):808-14 - PubMed
  33. Ann N Y Acad Sci. 2011 Jan;1217:139-53 - PubMed
  34. Cytometry A. 2008 Nov;73(11):975-83 - PubMed
  35. Cancer Immunol Immunother. 1990;31(2):121-7 - PubMed
  36. Nat Immunol. 2003 Dec;4(12):1191-8 - PubMed
  37. Immunity. 2007 Oct;27(4):670-84 - PubMed
  38. J Exp Med. 2007 Aug 6;204(8):1945-57 - PubMed
  39. Crit Rev Immunol. 2008;28(2):109-26 - PubMed
  40. J Immunol. 2010 Sep 15;185(6):3174-83 - PubMed
  41. Immunity. 2009 Nov 20;31(5):834-44 - PubMed
  42. J Clin Invest. 2007 Aug;117(8):2197-204 - PubMed
  43. J Exp Med. 2007 Sep 3;204(9):2015-21 - PubMed
  44. J Immunol. 2009 Mar 1;182(5):2786-94 - PubMed
  45. J Immunother. 2007 Jan;30(1):40-53 - PubMed
  46. Ann Oncol. 2006 Apr;17(4):563-70 - PubMed
  47. Nat Med. 2005 Dec;11(12):1299-305 - PubMed
  48. Nat Immunol. 2010 Feb;11(2):114-20 - PubMed
  49. J Exp Med. 2003 Aug 18;198(4):569-80 - PubMed
  50. Immunity. 2010 Jul 23;33(1):128-40 - PubMed
  51. Curr Drug Metab. 2008 Feb;9(2):167-74 - PubMed
  52. Nature. 2008 Mar 20;452(7185):356-60 - PubMed
  53. Science. 2007 Aug 3;317(5838):622-5 - PubMed
  54. N Engl J Med. 2011 Jun 30;364(26):2517-26 - PubMed
  55. Nat Immunol. 2001 May;2(5):423-9 - PubMed
  56. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):644-53 - PubMed
  57. Science. 2008 Feb 8;319(5864):822-5 - PubMed
  58. Semin Immunol. 2009 Apr;21(2):62-8 - PubMed
  59. J Immunol. 2011 May 1;186(9):5068-77 - PubMed

Publication Types

Grant support