Adoptive Cell Therapy for the Treatment of Patients with Metastatic Melanoma

Overview

Journal Curr Opin Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2009 Mar 24

PMID 19304471

Citations 276

Authors

Steven A Rosenberg

Mark E Dudley

Affiliations

Soon will be listed here.

Abstract

Adoptive cell therapy (ACT) is the best available treatment for patients with metastatic melanoma. In a recent series of three consecutive clinical trials using increasing lymphodepletion before infusion of autologous tumor infiltrating lymphocytes (TIL), objective response rates between 49% and 72% were seen. Persistence of infused cells in the circulation at one month was highly correlated with anti-tumor response as was the mean telomere length of the cells infused and the number of CD8+ CD27+ cells infused. Responses occur at all sites and appear to be durable with many patients in ongoing response beyond three years. In the most recent trial of 25 patients receiving maximum lymphodepletion, seven of the 25 patients (28%) achieved a complete response. Of the 12 patients in the three trials who achieved a complete response all but one are ongoing between 18 and 75 months. We recently demonstrated that ACT using autologous lymphocytes genetically modified to express anti-tumor T cell receptors can mediate tumor regression and this approach is now being applied to patients with common epithelial cancers.

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References

Gattinoni L, Finkelstein S, Klebanoff C, Antony P, Palmer D, Spiess P . Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005; 202(7):907-12. PMC: 1397916. DOI: 10.1084/jem.20050732. View

Rosenberg S, Restifo N, Yang J, Morgan R, Dudley M . Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008; 8(4):299-308. PMC: 2553205. DOI: 10.1038/nrc2355. View

Dudley M, Wunderlich J, Shelton T, Even J, Rosenberg S . Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother. 2003; 26(4):332-42. PMC: 2305721. DOI: 10.1097/00002371-200307000-00005. View

Tran K, Zhou J, Durflinger K, Langhan M, Shelton T, Wunderlich J . Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy. J Immunother. 2008; 31(8):742-51. PMC: 2614999. DOI: 10.1097/CJI.0b013e31818403d5. View

Paulos C, Wrzesinski C, Kaiser A, Hinrichs C, Chieppa M, Cassard L . Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J Clin Invest. 2007; 117(8):2197-204. PMC: 1924500. DOI: 10.1172/JCI32205. View

Huang J, Kerstann K, Ahmadzadeh M, Li Y, El-Gamil M, Rosenberg S . Modulation by IL-2 of CD70 and CD27 expression on CD8+ T cells: importance for the therapeutic effectiveness of cell transfer immunotherapy. J Immunol. 2006; 176(12):7726-35. PMC: 1532931. DOI: 10.4049/jimmunol.176.12.7726. View

Dudley M, Yang J, Sherry R, Hughes M, Royal R, Kammula U . Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008; 26(32):5233-9. PMC: 2652090. DOI: 10.1200/JCO.2008.16.5449. View

Robbins P, Li Y, El-Gamil M, Zhao Y, Wargo J, Zheng Z . Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions. J Immunol. 2008; 180(9):6116-31. PMC: 2424230. DOI: 10.4049/jimmunol.180.9.6116. View

Klebanoff C, Gattinoni L, Torabi-Parizi P, Kerstann K, Cardones A, Finkelstein S . Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci U S A. 2005; 102(27):9571-6. PMC: 1172264. DOI: 10.1073/pnas.0503726102. View

10.

Zhou J, Dudley M, Rosenberg S, Robbins P . Selective growth, in vitro and in vivo, of individual T cell clones from tumor-infiltrating lymphocytes obtained from patients with melanoma. J Immunol. 2004; 173(12):7622-9. PMC: 2174603. DOI: 10.4049/jimmunol.173.12.7622. View

11.

Gattinoni L, Klebanoff C, Palmer D, Wrzesinski C, Kerstann K, Yu Z . Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Invest. 2005; 115(6):1616-26. PMC: 1137001. DOI: 10.1172/JCI24480. View

12.

Rosenberg S, Yang J, Topalian S, Schwartzentruber D, Weber J, Parkinson D . Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994; 271(12):907-13. View

13.

Dudley M, Wunderlich J, Robbins P, Yang J, Hwu P, Schwartzentruber D . Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002; 298(5594):850-4. PMC: 1764179. DOI: 10.1126/science.1076514. View

14.

Dudley M, Wunderlich J, Yang J, Sherry R, Topalian S, Restifo N . Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005; 23(10):2346-57. PMC: 1475951. DOI: 10.1200/JCO.2005.00.240. View

15.

Rosenberg S, Packard B, Aebersold P, Solomon D, Topalian S, TOY S . Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988; 319(25):1676-80. DOI: 10.1056/NEJM198812223192527. View

16.

Rosenberg S, Yang J, Restifo N . Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004; 10(9):909-15. PMC: 1435696. DOI: 10.1038/nm1100. View

17.

Zhou J, Dudley M, Rosenberg S, Robbins P . Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother. 2004; 28(1):53-62. PMC: 2175172. DOI: 10.1097/00002371-200501000-00007. View

18.

Griffith K, Read E, Carrasquillo J, Carter C, Yang J, Fisher B . In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma. J Natl Cancer Inst. 1989; 81(22):1709-17. DOI: 10.1093/jnci/81.22.1709. View

19.

Aebersold P, Hyatt C, Johnson S, Hines K, Korcak L, Sanders M . Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response. J Natl Cancer Inst. 1991; 83(13):932-7. DOI: 10.1093/jnci/83.13.932. View

20.

Robbins P, Dudley M, Wunderlich J, El-Gamil M, Li Y, Zhou J . Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol. 2004; 173(12):7125-30. PMC: 2175171. DOI: 10.4049/jimmunol.173.12.7125. View