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

Cancer Discovery - Tập 8 Số 10 - Trang 1258-1269 - 2018
Matthew J. Frank1, Patrick M. Reagan2, Nancy L. Bartlett3, Leo I. Gordon4, Jonathan W. Friedberg2, Debra K. Czerwinski1, Steven Long1, Richard T. Hoppe5, Robert Janssen6, Albert F. Candia6, Robert L. Coffman6, Ronald Levy1
11Stanford University Hospital and Clinics, Division of Oncology, Stanford, California.
22University of Rochester Medical Center, Rochester, New York.
33Washington University School of Medicine, Siteman Cancer Center, St. Louis, Missouri.
44Feinberg School of Medicine, Northwestern University and the Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
55Stanford University Hospital and Clinics, Department of Radiation Oncology, Stanford, California.
66Dynavax Technologies Corporation, Berkeley, California.

Tóm tắt

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

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Cancer Discovery

Tập 8 Số 10

1258-1269

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