Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma

Kimberly A. Noonan, Carol A. Huff, Janice Davis, M. Victor Lemas, Susan Fiorino, Jeffrey Bitzan, Anna Ferguson, Amy Emerling, Leo Luznik, William Matsui, Jonathan Powell, Ephraim Fuchs, Gary L. Rosner, Caroline Epstein, Lakshmi Rudraraju, Richard F. Ambinder, Richard J. Jones, Drew Pardoll, Ivan Borrello

Research output: Contribution to journalArticle

Abstract

Successful adoptive T cell therapy (ACT) requires the ability to activate tumor-specific T cells with the ability to traffic to the tumor site and effectively kill their target as well as persist over time. We hypothesized that ACT using marrow-infiltrating lymphocytes (MILs) in multiple myeloma (MM) could impart greater antitumor immunity in that they were obtained from the tumor microenvironment. We describe the results from the first clinical trial using MILs in MM. Twenty-five patients with either newly diagnosed or relapsed disease had their MILs harvested, activated and expanded, and subsequently infused on the third day after myeloablative therapy. Cells were obtained and adequately expanded in all patients with anti-CD3/CD28 beads plus interleukin-2, and a median of 9.5 × 108 MILs were infused. Factors indicative of response to MIL ACT included (i) the presence of measurable myeloma-specific activity of the ex vivo expanded product, (ii) low endogenous bone marrow T cell interferon-γ production at baseline, (iii) a CD8+ central memory phenotype at baseline, and (iv) the generation and persistence of myeloma-specific immunity in the bone marrow at 1 year after ACT. Achieving at least a 90% reduction in disease burden significantly increased the progression-free survival (25.1 months versus 11.8 months; P = 0.01). This study demonstrates the feasibility and efficacy of MILs as a form of ACT with applicability across many hematologic malignancies and possibly solid tumors infiltrating the bone marrow.

Original languageEnglish (US)
JournalScience translational medicine
Volume7
Issue number288
DOIs
StatePublished - May 20 2015

ASJC Scopus subject areas

  • Medicine(all)

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