In situ vaccination with a tlr9 agonist and local low-dose radiation induces systemic responses in untreated indolent lymphoma

Matthew J. Frank, Patrick M. Reagan, Nancy L. Bartlett, Leo I. Gordon, Jonathan W. Friedberg, Debra K. Czerwinski, Steven R. Long, Richard T. Hoppe, Robert Janssen, Albert F. Candia, Robert L. Coffman, Ronald Levy

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

This multicenter phase I/II clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. Twenty-nine enrolled patients received 4 Gy of radiation followed by 5 weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their nontreated sites, with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T cells and decreases of T follicular helper and T regulatory cells (Treg) were observed in the tumor microenvironment. Low pretreatment levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease. SIGNIFICANCE: In situ vaccination with the TLR9 agonist SD-101, along with low-dose radiation, was safe and induced systemic responses in patients with indolent lymphoma. Low levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells in the tumor microenvironment predicted favorable response to treatment.

Original languageEnglish
Pages (from-to)1258-1269
Number of pages12
JournalCancer discovery
Volume8
Issue number10
DOIs
StatePublished - Oct 2018

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