In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase I/II study
Mené sur 15 patients atteints d'une forme rare de lymphome cutané à cellules T, cet essai de phase I/II évalue l'efficacité, la tolérabilité et la toxicité d'un traitement combinant une vaccination par injection intratumorale d'un agoniste du récepteur TLR9, impliqué dans la réponse immunitaire innée, avec une radiothérapie
We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenecity 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. Since 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 Tregs and a similar reduction in S100+, CD1a+ dendritic cells (DCs). There was a trend towards greater reduction of CD25+ T-cells and skin DCs in clinical responders vs. non-responders. 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.