In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma

Cancer Discov. 2018 Oct;8(10):1258-1269. doi: 10.1158/2159-8290.CD-18-0743. Epub 2018 Aug 28.

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. Cancer Discov; 8(10); 1258-69. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Immunotherapy / methods*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / radiotherapy*
  • Male
  • Middle Aged
  • Toll-Like Receptor 9 / metabolism*
  • Vaccination
  • Young Adult

Substances

  • Toll-Like Receptor 9