Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients

Laszlo G. Radvanyi, Chantale Bernatchez, Minying Zhang, Patricia S. Fox, Priscilla Miller, Jessica Chacon, Richard Wu, Gregory Lizee, Sandy Mahoney, Gladys Alvarado, Michelle Glass, Valen E. Johnson, John D. McMannis, Elizabeth Shpall, Victor Prieto, Nicholas Papadopoulos, Kevin Kim, Jade Homsi, Agop Bedikian, Wen Jen HwuSapna Patel, Merrick I. Ross, Jeffrey E. Lee, Jeffrey E. Gershenwald, Anthony Lucci, Richard Royal, Janice N. Cormier, Michael A. Davies, Rahmatu Mansaray, Orenthial J. Fulbright, Christopher Toth, Renjith Ramachandran, Seth Wardell, Audrey Gonzalez, Patrick Hwu

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

Purpose: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. Results: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T cells in the infusion product, a more differentiated effector phenotype of the CD8+ population, and a higher frequency of CD8+ T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. Conclusion: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8+ T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.

Original languageEnglish (US)
Pages (from-to)6758-6770
Number of pages13
JournalClinical Cancer Research
Volume18
Issue number24
DOIs
StatePublished - Dec 15 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients'. Together they form a unique fingerprint.

  • Cite this

    Radvanyi, L. G., Bernatchez, C., Zhang, M., Fox, P. S., Miller, P., Chacon, J., Wu, R., Lizee, G., Mahoney, S., Alvarado, G., Glass, M., Johnson, V. E., McMannis, J. D., Shpall, E., Prieto, V., Papadopoulos, N., Kim, K., Homsi, J., Bedikian, A., ... Hwu, P. (2012). Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clinical Cancer Research, 18(24), 6758-6770. https://doi.org/10.1158/1078-0432.CCR-12-1177