Number of the records: 1
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses
- 1.
SYSNO ASEP 0523540 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses Author(s) Dölen, Y. (NL)
Valente, M. (NL)
Tagit, O. (NL)
Jäger, Eliezer (UMCH-V) ORCID, RID
van Dinther, E. A. W. (NL)
van Riessen, N. K. (NL)
Hrubý, Martin (UMCH-V) RID, ORCID
Gileadi, U. (GB)
Cerundolo, V. (GB)
Figdor, C. G. (NL)Article number 1738813 Source Title Oncoimmunology - ISSN 2162-402X
Roč. 9, č. 1 (2020), s. 1-14Number of pages 14 s. Language eng - English Country GB - United Kingdom Keywords cancer vaccines ; nanoparticle biodistribution ; iNKT cells Subject RIV CD - Macromolecular Chemistry OECD category Polymer science R&D Projects GA17-07164S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UMCH-V - RVO:61389013 UT WOS 000519983200001 EID SCOPUS 85081903652 DOI 10.1080/2162402X.2020.1738813 Annotation Nanovaccines, co-delivering antigen and invariant natural killer T (iNKT) cell agonists, proved to be very effective in inducing anti-tumor T cell responses due to their exceptional helper function. However, it is known that iNKT cells are not equally present in all lymphoid organs and nanoparticles do not get evenly distributed to all immune compartments. In this study, we evaluated the effect of the vaccination route on iNKT cell help to T and B cell responses for the first time in an antigen and agonist co-delivery setting. Intravenous administration of PLGA nanoparticles was mainly targeting liver and spleen where iNKT1 cells are abundant and induced the highest serum IFN-y levels, T cell cytotoxicity, and Th-1 type antibody responses. In comparison, after subcutaneous or intranodal injections, nanoparticles mostly drained or remained in regional lymph nodes where iNKT17 cells were abundant. After subcutaneous and intranodal injections, antigen-specific IgG2 c production was hampered and IFN-y production, as well as cytotoxic T cell responses, depended on sporadic systemic drainage. Therapeutic anti-tumor experiments also demonstrated a clear advantage of intravenous injection over intranodal or subcutaneous vaccinations. Moreover, tumor control could be further improved by PD-1 immune checkpoint blockade after intravenous vaccination, but not by intranodal vaccination. Anti PD-1 antibody combination mainly exerts its effect by prolonging the cytotoxicity of T cells. Nanovaccines also demonstrated synergism with anti-4-1BB agonistic antibody treatment in controlling tumor growth. We conclude that nanovaccines containing iNKT cell agonists shall be preferentially administered intravenously, to optimally reach cellular partners for inducing effective anti-tumor immune responses. Workplace Institute of Macromolecular Chemistry Contact Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Year of Publishing 2021 Electronic address https://www.tandfonline.com/doi/full/10.1080/2162402X.2020.1738813
Number of the records: 1