Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma

Nela Klein-González Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia;[email protected]

Udo Holtick Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia; Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia

Kirsten Fairfax Laboratory for Transplantation and Tumor Immunology, Max Eder Group, University of Cologne, Germany; Department of Medicine (Cancer Research), West German Cancer Center, University of Essen, Germany; Laboratory for Transplantation and Tumor Immunology, Max Eder Group, University of Cologne, Germany; Department of Medicine (Cancer Research), West German Cancer Center, University of Essen, Germany

Martin R Weihrauch Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia; Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia

Michael S von Bergwelt-Baildon Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia; Department I for Internal Medicine, Hematology, Oncology, University of Cologne, Germany; Immunology Department, Central Clinical School, Monash University, Melbourne, Australia

Abstract

Evaluation of: Brody JD, Ai WZ, Czerwinski DK et al.In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a Phase I/II study. J. Clin. Oncol. 28(28), 4324–4332 (2010).

Despite high response rates of the follicular B-cell lymphoma to monoclonal antibodies, the clinical course of lymphoma is still characterized by a continuous pattern of relapse. Brody and colleagues treated 15 patients with relapsed, low-grade lymphoma using low-dose radiotherapy applied to one of the tumor sites with combined injection of a TLR-9 agonist at the same site. This strategy induced specific immunity and tumor regression in several patients with an objective response rate of 27%. The results indicate an involvement of the tumor TLR-9-expressing B cells acting as antigen-presenting cells. TLR-9 in situ vaccination combined with local radiotherapy clearly warrants further in-depth analysis and investigation in a Phase III randomized trial, and may provide a new opportunity for the treatment of B-cell malignancies.

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Financial & competing interests disclosure

Martin R Weihrauch is a member of the scientific advisory board of Mologen AG, Berlin, Germany. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma

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Targeting malignant B cells as antigen-presenting cells: TLR-9 agonist induces systemic regression of lymphoma

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