Abstract
AbstractWe have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8+ T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25+, Foxp3+ T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100+, CD1a+ dendritic cells. There was a trend toward greater reduction of CD25+ T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.
Highlights
We have demonstrated that an in situ vaccination strategy using low-dose local radiation therapy (RT) bracketed with intratumoral injection of CpG is feasible and safe in patients with mycosis fungoides (MF)
The most common toxicities were expected from past experience, including injection site reactions and flu-like symptoms.[12]
Objective systemic clinical responses were noted in one third of enrolled patients
Summary
Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25؉, Foxp3؉ T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100؉, CD1a؉ dendritic cells. There was a trend toward greater reduction of CD25؉ T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993. This study is registered at www.clinicaltrials.gov as NCT00226993. (Blood. 2012;119(2): 355-363)
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