Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity

Farideh Ordikhani, Mayuko Uehara, Vivek Kasinath, Li Dai, Siawosh K. Eskandari, Baharak Bahmani, Merve Yonar, Jamil R. Azzi, Yousef Haik, Peter T. Sage, George F. Murphy, Nasim Annabi, Tobias Schatton, Indira Guleria, Reza Abdi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti-PD-1 antibody encapsulated in PLGA nanoparticles (anti-PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti-PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti-PD-1 antibody, due to the overactivation of T cells. Administration of anti-PD-1 NPs to splenectomized LT-α-/- mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti-PD-1-associated toxicity. Attenuation of the anti-PD-1 NPs dosage prevented toxicity and significantly improved its antitumor effect in the B16-F10 murine melanoma model. Furthermore, we found that anti-PD-1 NPs undergo internalization by DCs in the spleen, leading to their maturation and the subsequent activation of T cells. Our findings provide important clues that can lead to the development of strategies to enhance the efficacy of immune checkpoint inhibitors.

Original languageEnglish
JournalJCI insight
Volume3
Issue number20
DOIs
Publication statusPublished - 18 Oct 2018

Fingerprint

Antigen-Presenting Cells
Nanoparticles
Immunity
Spleen
Antineoplastic Agents
T-Lymphocytes
Mortality
Antibodies
Lymphoid Tissue
Melanoma
Lymph Nodes
Research
Neoplasms

Keywords

  • Cancer immunotherapy
  • Immunology

Cite this

Ordikhani, F., Uehara, M., Kasinath, V., Dai, L., Eskandari, S. K., Bahmani, B., ... Abdi, R. (2018). Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity. JCI insight, 3(20). https://doi.org/10.1172/jci.insight.122700

Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity. / Ordikhani, Farideh; Uehara, Mayuko; Kasinath, Vivek; Dai, Li; Eskandari, Siawosh K.; Bahmani, Baharak; Yonar, Merve; Azzi, Jamil R.; Haik, Yousef; Sage, Peter T.; Murphy, George F.; Annabi, Nasim; Schatton, Tobias; Guleria, Indira; Abdi, Reza.

In: JCI insight, Vol. 3, No. 20, 18.10.2018.

Research output: Contribution to journalArticle

Ordikhani, F, Uehara, M, Kasinath, V, Dai, L, Eskandari, SK, Bahmani, B, Yonar, M, Azzi, JR, Haik, Y, Sage, PT, Murphy, GF, Annabi, N, Schatton, T, Guleria, I & Abdi, R 2018, 'Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity', JCI insight, vol. 3, no. 20. https://doi.org/10.1172/jci.insight.122700
Ordikhani F, Uehara M, Kasinath V, Dai L, Eskandari SK, Bahmani B et al. Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity. JCI insight. 2018 Oct 18;3(20). https://doi.org/10.1172/jci.insight.122700
Ordikhani, Farideh ; Uehara, Mayuko ; Kasinath, Vivek ; Dai, Li ; Eskandari, Siawosh K. ; Bahmani, Baharak ; Yonar, Merve ; Azzi, Jamil R. ; Haik, Yousef ; Sage, Peter T. ; Murphy, George F. ; Annabi, Nasim ; Schatton, Tobias ; Guleria, Indira ; Abdi, Reza. / Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity. In: JCI insight. 2018 ; Vol. 3, No. 20.
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