Ed by intratumoral administration of VSV-IFN major to tumor regression, prolonged survival, and remedy in 30 of immunized syngeneic LM2 lung tumors [148]. Melanoma is an indication that has been frequently visited for vaccine development applying viral vectors [178]. As an example, immunization of C57BL/6 mice carrying B16-OVA melanoma tumors with KUN-GM-CSF particles resulted in substantial tumor regression and remedy of greater than 50 of treated animals [138]. GYY4137 site Furthermore, expression of the chicken ovalbumin (OVA) cytotoxic T cell lymphocyte (CTL) epitope SIINFEKL from an YFV vector induced SIINFEKL-specific CD8 lymphocytes and provided protection against challenges with B16-OVA or B16F0 melanoma cells in immunized C57BL/6 mice [149]. Alphaviruses have also been employed for melanoma therapy. For instance, humoral immune responses, anti-tumor activity, and prolonged survival were obtained inside a B16 mouse melanoma model following immunization with VEEV particles expressing the tyrosine-related protein-2 (TRP-2) [150]. In a further approach, VEEV-TRP-2 particles have been combined with antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced tumor necrosis element receptor (GITR) monoclonal antibodies (mAbs) [151]. Immunization with VEEV-TRP-2 and anti-GITR mAbs induced complete tumor regression in 90 of mice, whereas VEEV-TRP-2 and anti-CTLA-4 SB 271046 manufacturer therapy resulted in tumor shrinkage in 50 of animals. Within the context of DNA-based delivery, SFV DNA replicons expressing VEGFR-2 and IL-12 from one plasmid vector and survivin and -hCG antigens from one more plasmid were co-administered to mice with implanted B16 melanoma tumors [152]. The mixture immunization offered superior tumor growth inhibition and prolonged survival when compared with administration of either SFV DNA replicon alone. In the case of MV vectors, the oncolytic potential in the MV Leningrad-16 (L-16) strain was demonstrated to provide effective killing of tumor cells and inhibition of tumor growth within the mel Z mouse melanoma model [153]. Associated with VSV, a pseudotyped vector, where the VSV-G protein was replaced by the non-neurotropic lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP), showed efficacy in subcutaneous A375 xenograft and B16-OVA syngeneic mouse tumor models, as well as reduced the size of lung metastasis following systemic therapy [154].Vaccines 2021, 9,18 ofIn the context of ovarian cancer, the pseudotyped VSV-LCMV-GP vector showed oncolytic activity against A2780, HOC7, SKOV6 as well as other ovarian cancer cell lines and in vivo inside the A2780 ovarian mouse tumor model [155]. Tumor regression was further enhanced by combination therapy with all the JAK1/2 inhibitor ruxolitinib. MV vectors have also been evaluated for ovarian cancer therapy. Tumor-specific targeting has been achieved by engineering in the MV-FR vector using a single-chain antibody (scFV) sequence for the alpha-folate receptor (FR) [156]. Intratumoral injection of MV-FR into mice with ovarian SKOV3ip.1 xenografts demonstrated lowered tumor volumes and prolonged all round survival. Furthermore, MV-CEA and MV-NIS have been applied alone or in combination for immunization of mice implanted with SKOV3ip.1 xenografts [157]. The dual therapy was superior to either MV-CEA or MV-NIS treatment alone. The MV-CEA vector has been evaluated in a phase I clinical trial in patients with taxol and platinum-refractory recurrent ovarian cancer (RROC) [173]. The study demonstrated that intraperitoneal administration of MV-CEA wa.