Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses
Autor: | Michael Valente, Eliézer Jäger, N. Koen van Riessen, Eric A. W. van Dinther, Uzi Gileadi, Carl G. Figdor, Martin Hruby, Vincenzo Cerundolo, Oya Tagit, Yusuf Dolen |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
T cell Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Immunology Cell Biology Cancer vaccines Antibodies 4-1BB nanoparticle biodistribution 03 medical and health sciences 0302 clinical medicine All institutes and research themes of the Radboud University Medical Center Antigen Neoplasms PD-1 medicine Immunology and Allergy Humans RC254-282 B cell iNKT cells Antitumor activity B-Lymphocytes Neoplasms. Tumors. Oncology. Including cancer and carcinogens INKT Cells RC581-607 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis checkpoint blockade Natural Killer T-Cells Immunologic diseases. Allergy Back Matter |
Zdroj: | Oncoimmunology, 9 Oncoimmunology, 9, 1 OncoImmunology Oncoimmunology article-version (VoR) Version of Record OncoImmunology, Vol 9, Iss 1 (2020) |
ISSN: | 2162-4011 |
Popis: | 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. |
Databáze: | OpenAIRE |
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