Single low-dose cyclophosphamide combined with interleukin-12 gene therapy is superior to a metronomic schedule in inducing immunity against colorectal carcinoma in mice
- Malvicini, Mariana
- Alaniz, Laura Daniela
- Bayo Fina, Juan Miguel
- García, Mariana Gabriela
- Piccioni, Flavia Valeria
- Fiore, Esteban Juan
- Atorrasagasti, María Catalina
- Aquino, Jorge Benjamin
- Matar, Pablo
- Mazzolini Rizzo, Guillermo Daniel
DOIAbstract
The use of conventional cytotoxic agents at metronomic schedules, alone or in combination with targeted agents or immunotherapy, is being explored as a promising anticancer strategy. We previously reported a potent antitumor effect of a single low-dose cyclophosphamide and interleukin-12 (IL-12) gene therapy against advanced gastrointestinal carcinoma, in mice. Here, we assessed whether the delivery of IL-12 by gene therapy together with metronomic cyclophosphamide exerts antitumor effects in a murine model of colorectal carcinoma. This combination therapy was able, at least in part, to reverse immunosuppression, by decreasing the number of regulatory T cells (Tregs) as well as of splenic myeloid-derived suppressor cells (MDSC s). However, ...
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