pVAX14DNA-mediated add-on immunotherapy combined with arsenic trioxide and all-trans retinoic acid targeted therapy effectively increases the survival of acute promyelocytic leukemia mice

摘要

Novel immunotherapeutic approaches have recently highlighted the benefit of adjuvant add-on immunotherapy approaches combined with chemotherapy or targeted therapies. To validate this approach, we took advantage of a mouse transplantable acute promyelocytic leukemia (APL) model 1 that has proven to be a very robust and reproducible in viv o pre-clinical model of all the current and prospective therapeutic approaches of this leukemia as a proof-on concept for other malignancies. 2 Of relevance to this study, this model was used to demonstrate a synergy of all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) for APL eradication and elucidate its mechanism of action, 3 and this strategy is used as targeted therapies for patients. 4 , 5 , 6 Using this preclinical model, we previously demonstrated the efficacy of combined fusion gene promyelocytic leukemia-retonoic acid receptor alpha (PML-RARA) DNA administration with ATRA on mouse survival and leukemia-initiating cell eradication. 7 , 8 , 9 , 10 , 11 We have recently reported the similar efficacy of a novel nonspecific DNA construct pVAX14 with adjuvant properties and with an equally effective impact on the survival of these APL mice in combination with ATRA. 8 More recently, ATRA combined with ATO has become the reference treatment for newly diagnosed APL. 4 Thus, this present study focused on the therapeutic potential of pVAX14 to increase the efficacy of the combination ATO+ATRA treatment (schematic diagram of the protocol described in Figure 1a ).