CLINICAL TRIALS AND OBSERVATIONS In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9

We have developed and previously re-ported on a therapeutic vaccination strat-egy for indolent B-cell lymphoma that combines local radiation to enhance tu-mor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8 T cells are in-duced, and systemic tumor regression was documented. Because the vaccina-tion 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 re-sponses 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 re-duction of CD25, Foxp3 T cells that could be either MF cells or tissue regula-tory 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 aug-ment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993. (Blood. 2012;119(2): 355-363