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BioDrugs

, Volume 28, Issue 5, pp 421–437 | Cite as

Tumor-Infiltrating Lymphocyte Therapy for Melanoma: Rationale and Issues for Further Clinical Development

  • Geok Choo Sim
  • Jessica Chacon
  • Cara Haymaker
  • Krit Ritthipichai
  • Manish Singh
  • Patrick Hwu
  • Laszlo Radvanyi
Review Article

Abstract

Cancer immunotherapy has become an important area for the future development of cancer therapy; this includes T-cell-based therapies that involve adoptive transfer of autologous T cells derived from the tumors or peripheral blood of cancer patients, vaccines, oncolytic virus therapy, and immunomodulatory antibodies and ligands. Here, we summarize the current approaches and clinical data in the field of adoptive T-cell transfer therapy using tumor-infiltrating lymphocytes (TILs) for metastatic melanoma. We also discuss current knowledge on the mechanism of transferred TILs in mediating tumor regression and the growing need for and recent advances in the identification of predictive biomarkers to better select patients for TIL therapy. The current technical limitations of current TIL expansion methods for out-scaling are discussed as well as how these are being addressed in order to further “industrialize” this form of cell therapy. Lastly, how TIL adoptive transfer can be incorporated into the current melanoma treatment continuum, especially as combination therapy with other immunomodulators and targeted drugs, is discussed.

Keywords

Melanoma Telomere Length Melanoma Patient Ipilimumab Adoptive Cell Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments and Disclosures

The authors have declared that no conflict of interest exists. This work is supported by NIH research grants 1R21CA178580-01, 1RO1 CA111999-01A2, and 5 P0 CA093459-05-DRP21, and grants from the Melanoma Research Alliance, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF), and the Gillson Longenbough Foundation. Support from a multi-investigator grant (RP110553 P4 01) from the Cancer Prevention and Research Institute of Texas (CPRIT) is also acknowledged. We would like to thank the members of the surgical staff, melanoma medical oncology nurses and physicians, and pathology staff for their contribution to the success of the TIL therapy program at the MD Anderson Cancer Center (Houston, TX, USA). We also would like to thank our “TIL Lab” members, including Chantale Bernatchez, Rhamatu Mansaray, Orenthial J. Fulbright, Christopher Toth, Renjith Ramachandran, Seth Wardell, Audrey Gonzalez, Kathryn Bushnell, and Marissa Gonzalez, for their hard work and contribution to the TIL therapy program.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Geok Choo Sim
    • 1
  • Jessica Chacon
    • 1
  • Cara Haymaker
    • 1
  • Krit Ritthipichai
    • 1
  • Manish Singh
    • 2
  • Patrick Hwu
    • 1
  • Laszlo Radvanyi
    • 1
  1. 1.Department of Melanoma Medical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Lion BiotechnologiesWoodland HillsUSA

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