PMID- 32000913 OWN - NLM STAT- MEDLINE DCOM- 20201218 LR - 20201218 IS - 1557-7988 (Electronic) IS - 0076-6879 (Linking) VI - 632 DP - 2020 TI - Recombinant fusion proteins for targeting dendritic cell subsets in therapeutic cancer vaccine. PG - 521-543 LID - S0076-6879(19)30470-7 [pii] LID - 10.1016/bs.mie.2019.11.013 [doi] AB - Dendritic cells (DCs) are professional antigen-presenting cells, which are optimal for the priming of a T cell response against pathogens and tumors. Therefore, many efforts are made to develop therapeutic cancer vaccines which preferentially target the antigen to DC subsets. To this aim, we developed two types of recombinant fusion proteins, which favor antigen delivery to pro-inflammatory DCs as well as the crosstalk between specialized subpopulations of DCs. The first approach combines peptide/CpG vaccination with the recruitment of iNKT cells to the tumor site via CD1d-antitumor scFv fusion proteins. The second approach is targeting the tumor antigen to cross-presenting Xcr1(+) DCs via a fusion protein made of Xcl1 fused to a synthetic long peptide followed by an IgG1 Fc fragment. Both strategies allow a potent tumor-specific CD8 T cell response associated with tumor regression or tumor growth delay depending on the model. In the case of iNKT cell activation, the strategy relies on a strong IL-12 release by splenic DCs, while in the second case, the T cell response is strictly dependent on the presence of Xcr1(+) cross-presenting DCs. CI - (c) 2020 Elsevier Inc. All rights reserved. FAU - Corgnac, Stephanie AU - Corgnac S AD - Department of Fundamental Oncology, Faculty of Biology and Medicine, University of Lausanne, Epalinges, Switzerland; INSERM UMR 1186, Integrative Tumor Immunology and Genetic Oncology, Gustave Roussy, EPHE, PSL, Fac. de Medecine-Univ. Paris-Sud, Universite Paris-Saclay, Villejuif, France. FAU - Botelho, Natalia K AU - Botelho NK AD - Department of Fundamental Oncology, Faculty of Biology and Medicine, University of Lausanne, Epalinges, Switzerland. FAU - Donda, Alena AU - Donda A AD - Department of Fundamental Oncology, Faculty of Biology and Medicine, University of Lausanne, Epalinges, Switzerland. Electronic address: alena.donda@unil.ch. FAU - Romero, Pedro AU - Romero P AD - Department of Fundamental Oncology, Faculty of Biology and Medicine, University of Lausanne, Epalinges, Switzerland. LA - eng PT - Journal Article DEP - 20191218 PL - United States TA - Methods Enzymol JT - Methods in enzymology JID - 0212271 RN - 0 (Cancer Vaccines) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes/immunology MH - Cancer Vaccines/immunology/*therapeutic use MH - Cross-Priming MH - Dendritic Cells/*immunology MH - HEK293 Cells MH - Humans MH - Killer Cells, Natural/immunology MH - Mice, Inbred C57BL MH - Neoplasms/immunology/*therapy MH - Recombinant Fusion Proteins/immunology/therapeutic use OTO - NOTNLM OT - CD1d OT - CD8+ T cell OT - Cross-presenting DC OT - Recombinant fusion protein OT - Tumor vaccine OT - Xcl1 OT - Xcr1+ DC OT - iNKT cell EDAT- 2020/02/01 06:00 MHDA- 2020/12/19 06:00 CRDT- 2020/02/01 06:00 PHST- 2020/02/01 06:00 [entrez] PHST- 2020/02/01 06:00 [pubmed] PHST- 2020/12/19 06:00 [medline] AID - S0076-6879(19)30470-7 [pii] AID - 10.1016/bs.mie.2019.11.013 [doi] PST - ppublish SO - Methods Enzymol. 2020;632:521-543. doi: 10.1016/bs.mie.2019.11.013. Epub 2019 Dec 18.