In Situ Vaccination with a TLR 9 Agonist and Local Low Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma. Cancer discovery Frank, M. J., Reagan, P. M., Bartlett, N. L., Gordon, L. I., Friedberg, J. W., Czerwinski, D. K., Long, S. R., Hoppe, R. T., Janssen, R. S., Candia, A. F., Coffman, R. L., Levy, R. 2018

Abstract

This multicenter phase 1/2 clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. 29 enrolled patients received 4 Gy of radiation followed by five 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 non-treated 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 (Tregs) were observed in the tumor microenvironment. Low pre-treatment levels of CD4+ Tregs, proliferating CD8+ T-cells, and GranzymeB+ 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.

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