Investigation of parameters that determine Nano-DC vaccine transport
Effective migration of dendritic cells into the lymphatic system organs is the prerequisite for a functional dendritic cell vaccine. We have previously developed a porous silicon microparticle (PSM)-based therapeutic dendritic cell vaccine (Nano-DC vaccine) where PSM serves both as the vehicle for antigen peptides and an adjuvant. Here, we analyzed parameters that determined dendritic cell uptake of PSM particles and Nano-DC vaccine accumulation in lymphatic tissues in a murine model of HER2-positive breast cancer. Our study revealed a positive correlation between sphericity of the PSM particles and their cellular uptake by circulating dendritic cells. In addition, the intravenously administered vaccines accumulated more in the spleens and inguinal lymph nodes, while the intradermally inoculated vaccines got enriched in the popliteal lymph nodes. Furthermore, mice with large tumors received more vaccines in the lymph nodes than those with small to medium size tumors. Information from this study will provide guidance on design and optimization of future therapeutic cancer vaccines.
KeywordsSilicon Microparticle Nano-DC vaccine Biodistribution Transport
This work was partially supported by National Institutes of Health grants R01CA193880, R01CA222959 and U54CA210181, US Department of Defense grant W81XWH-17-1-0389, and METAvivor.
- B.M. Carreno, V. Magrini, M. Becker-Hapak, S. Kaabinejadian, J. Hundal, A.A. Petti, A. Ly, W.R. Lie, W.H. Hildebrand, E.R. Mardis, G.P. Linette, Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science 348(6236), 803–808 (2015)CrossRefGoogle Scholar
- A.W. Li, M.C. Sobral, S. Badrinath, Y. Choi, A. Graveline, A.G. Stafford, J.C. Weaver, M.O. Dellacherie, T.Y. Shih, O.A. Ali, J. Kim, K.W. Wucherpfennig, D.J. Mooney, A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater. 17(6), 528–52+ (2018)CrossRefGoogle Scholar
- E.A. Mittendorf, G.T. Clifton, J.P. Holmes, K.S. Clive, R. Patil, L.C. Benavides, J.D. Gates, A.K. Sears, A. Stojadinovic, S. Ponniah, G.E. Peoples, Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: From US military Cancer institute clinical trials group study I-01 and I-02. Cancer 118(10), 2594–2602 (2012)CrossRefGoogle Scholar
- H. Shen, C. Rodriguez-Aguayo, R. Xu, V. Gonzalez-Villasana, J. Mai, Y. Huang, G. Zhang, X. Guo, L. Bai, G. Qin, X. Deng, Q. Li, D.R. Erm, B. Aslan, X. Liu, J. Sakamoto, A. Chavez-Reyes, H.D. Han, A.K. Sood, M. Ferrari, G. Lopez-Berestein, Enhancing chemotherapy response with sustained EphA2 silencing using multistage vector delivery. Clin. Cancer Res. 19(7), 1806–1815 (2013a)CrossRefGoogle Scholar
- J.L. Tanyi, S. Bobisse, E. Ophir, S. Tuyaerts, A. Roberti, R. Genolet, P. Baumgartner, B.J. Stevenson, C. Iseli, D. Dangaj, B. Czerniecki, A. Semilietof, J. Racle, A. Michel, I. Xenarios, C. Chiang, D.S. Monos, D.A. Torigian, H.L. Nisenbaum, O. Michielin, C.H. June, B.L. Levine, D.J. Powell Jr., D. Gfeller, R. Mick, U. Dafni, V. Zoete, A. Harari, G. Coukos, L.E. Kandalaft, Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci. Transl. Med. 10(436), eaao5931 (2018)CrossRefGoogle Scholar
- X. Xia, J. Mai, R. Xu, J.E. Perez, M.L. Guevara, Q. Shen, C. Mu, H.Y. Tung, D.B. Corry, S.E. Evans, X. Liu, M. Ferrari, Z. Zhang, X.C. Li, R.F. Wang, H. Shen, Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response. Cell Rep. 11, 957–966 (2015)CrossRefGoogle Scholar
- R. Xu, G. Zhang, J. Mai, X. Deng, V. Segura-Ibarra, S. Wu, J. Shen, H. Liu, Z. Hu, L. Chen, Y. Huang, E. Koay, Y. Huang, J. Liu, J.E. Ensor, E. Blanco, X. Liu, M. Ferrari, H. Shen, An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nat. Biotechnol. 34(4), 414–418 (2016)CrossRefGoogle Scholar
- H. Zong, S. Sen, G. Zhang, C. Mu, Z.F. Albayati, D.G. Gorenstein, X. Liu, M. Ferrari, P.A. Crooks, G.J. Roboz, H. Shen, M.L. Guzman, In vivo targeting of leukemia stem cells by directing parthenolide-loaded nanoparticles to the bone marrow niche. Leukemia 30(7), 1582–1586 (2016)CrossRefGoogle Scholar