Journal
CANCER DISCOVERY
Volume 8, Issue 10, Pages 1258-1269Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-18-0743
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Funding
- NCI [R35CA19735301]
- Dynavax Corporation
- American Cancer Society's Grand View League
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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. (C) 2018 AACR.
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