![]() In addition, co-delivery with immune adjuvant enables to reduce the dose of antigen 14. ![]() In vivo administration of immunoadjuvant with glycoprotein 100 (gp100), as a melanoma TAAs, effectively increased the efficacy of vaccination against selected TAA 12.Ĭo-delivery of TAAs with immune-inducing adjuvant like CpG-ODN to the same DCs efficiently enhance the uptake by DCs, accelerates the induction of the immune system, and extends the duration of the induced immune response 13. In most cases, peptides are routinely administered with an immune adjuvant 11. The weak immune responses to TAAs may be due to their physical size, which are typically below the desired size for efficient uptake by dendritic cells (DCs) 10. Indeed, many TAAs as peptide vaccine inducing CTL responses have been extensively researched 8, but most of them were self-antigens that faced significant barriers as immune tolerance 9, besides their poor immunogenicity. Successful anti-cancer immunotherapy is mainly dependent upon the presence and activation of antigen-specific cytotoxic T cells (CTLs) as essential arms in anti-cancer immunity 7 and IFN-γ production needed for amplifying T cell responses 1. There is emerging data pointing to the potential application of anti-cancer vaccines combined with monoclonal antibodies (mAb), resolving this obstacle 5, 6. Poor immunogenicity of tumor-associated antigens (TAAs) and immunosuppressive characteristic of TME may cause primary resistance to PD-1 therapy 4. Despite inducing potent and durable anti-tumor immunity, this approach has a limited function as monotherapy due to the lack of pre-existing T cell infiltration into the tumor microenvironment (TME), which leads to resistance to PD-1 blockade therapy 2, 3. Our results provide essential insights to devise combining regimens to improve the efficacy of immune checkpoint blockers even by a low dose of peptide and CpG-ODN.īlockade of an inhibitory checkpoint pathway such as programmed cell death protein 1 (PD-1) has significantly improved the current landscape of cancer immunotherapy 1. ![]() Furthermore, this combination also led to a remarkable tumor remission and prolonged survival rate in melanoma-bearing mice compared to non-liposomal peptide plus CpG-ODN or single-treated liposomal peptide formulations. Our results showed a combination of liposomal peptide plus CpG-ODN pulsed DC with anti-PD-1 antibody was more efficacious, as evidenced by a significant increase in T eff/T reg TILs with a marked fourfold elevation of IFN-γ expression level in the tumor site of treated mice which reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy. Lack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration.
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