Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy.

Abstract

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. 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. 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 Teff/Treg 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. 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 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.

• Authors: Mona Yazdani, Zahra Gholizadeh, Amin Reza Nikpoor, Nema Mohamadian Roshan, Mahmoud Reza Jaafari, Ali Badiee
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 14661 (07 19 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 34282215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• CPG-oligonucleotide
• Cancer Vaccines
• Immune Checkpoint Inhibitors
• Liposomes
• Oligodeoxyribonucleotides
• Programmed Cell Death 1 Receptor

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigens, Neoplasm (administration & dosage)
• Cancer Vaccines (administration & dosage)
• Combined Modality Therapy
• Dendritic Cells (transplantation)
• Dose-Response Relationship, Drug
• Female
• Immune Checkpoint Inhibitors (administration & dosage)
• Immunotherapy (methods)
• Immunotherapy, Adoptive (methods)
• Liposomes
• Mice
• Mice, Inbred C57BL
• Neoplasms (immunology, pathology, therapy)
• Oligodeoxyribonucleotides (administration & dosage)
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, immunology)
• Tumor Cells, Cultured