Vaccination of dendritic cells (DC) combined with
GM-CSF secreting
tumor cells has shown good therapeutic efficacy in several
tumor models. Nevertheless, the engineering of
GM-CSF secreting tumor cell line could represent a tedious step limiting its application for treatment in patients. We therefore developed in rats, an "all in vivo" strategy of combined vaccination using an in vivo local irradiation of the
tumor as a source of
tumor antigens for DC
vaccines and an exogenous source of
GM-CSF. We report here that supplying recombinant mGM-CSF by local
injections or surgical implantation of osmotic pumps did not allow reproducing the therapeutic efficacy observed with in vitro prepared
combined vaccines. To bypass this limitation possibly due to the short half-life of recombinant
GM-CSF, we have generated adeno-associated virus coding for mGM-CSF and tested their efficacy to transduce
tumor cells in vitro and in vivo. The in vivo
vaccines combining local irradiation and AAV2/1-mGM-CSF vectors showed high therapeutic efficacy allowing to cure 60% of the rats with pre-implanted
tumors, as previously observed with in vitro prepared
vaccines. Same efficacy has been observed with a second generation of
vaccines combining DC, local
tumor irradiation, and the controlled supply of recombinant mGM-CSF in
poloxamer 407, a biocompatible thermoreversible
hydrogel. By generating a successful "all in vivo" vaccination protocol combining
tumor radiotherapy with DC
vaccines and a straightforward supply of
GM-CSF, we have developed a therapeutic strategy easily translatable to clinic that could become accessible to a much bigger number of
cancer patients.