467119 Enhanced Cancer Immunotherapy By Microneedle Patch-Assisteddelivery of Anti-PD1 Antibody

Tuesday, November 15, 2016: 4:45 PM
Golden Gate 5 (Hilton San Francisco Union Square)
Yanqi Ye1, Chao Wang2, Gabrielle Hochu2, Hasan Sadeghifar3 and Zhen Gu2, (1)University of North Carolina at Chapel Hill, Chapel Hill, NC, (2)University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, (3)North Carolina State University, Raleigh, NC

Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody

Yanqi Yea, b, Chao Wanga, b, Gabrielle M. Hochua , Hasan Sadeghifarc, Zhen Gua, b, d *

a Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA;

b Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;

c Department of Forest Biomaterials, North Carolina State University, Raleigh, NC 27695, USA;

d Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA


Introduction: For skin cancer treatment, immunotherapies have been intensively studied over the past several years).[1,2,3] The anti-PD-1 antibodies that target the inhibitory receptors have shown striking antitumor activity in phase II and III clinical trials of advanced melanoma). Despite the exciting clinical results of anti-PD-1 antibodies for the treatment of melanoma, the efficacy of the approach remains to be improved.

Materials and Methods: Here we present the physiologically self-degradable MN patch-assisted cancer immunotherapy for controlled delivery of aPD1 toward melanoma (Figure 1). Each MN is composed of biocompatible hyaluronic acid (HA) integrated with NPs that encapsulate aPD1 and glucose oxidase (GOx).[4, 5] With the GOx/CAT enzymatic system immobilized inside the NPs, the enzyme-mediated generation of gluconic acid promotes the gradual self-dissociation of NPs and results in the sustained release of aPD1.

Results and Discussion: We show that a single administration of the MN patch induces robust immune responses in B16F10 mouse melanoma model exceeding MN in the absence of the trigger element (GOx) or intratumor injection of free aPD1. Moreover, we demonstrated that the MN coloaded with aCTLA-4 and aPD1 resulted in synergistic treatment of melanoma. These results demonstrate that the MN patch-assisted system provides an innovative delivery strategy of aPD1 via a simple and safe technique that improves cancer immunogenicity and facilitates the clinical treatment of melanoma.

Conclusions: We have developed the MN patch-assisted immunotherapy that delivers aPD1 for the enhanced treatment of the skin cancer. Additionally, MN severs as a platform for combined therapy with other immunomodulators to enhance immunotherapy efficiency

Acknowledgements: This work was supported by NC TraCS (grant 550KR51307), NIH's Clinical and Translational Science Awards (CTSA, 1UL1TR001111) at UNC-CH, the NC State Faculty Research and Professional Development Award, and start-up package from the Joint BME Department of UNC and NCSU to Z.G.


Figure 1. Schematic of the MN patch-assisted delivery of aPD1 for the skin cancer treatment. (a) MN patch loaded with self-dissociated NPs. (b) The blockade of PD-1.

 

 

References:

[1] Wang, C.; Ye, Y.; Gu, Z. et al. Nano Letters 2016.

[2] Sullivan, S. P.; Prausnitz, M. R. et al. Adv. Mater. 2008, 933−938.

[3] Gu, L.; Mooney, D. J. Nat. Rev. Cancer 2015, 56−66.

[4] Yu, J.; Zhang, Y.; Ye, Y., Gu, Z. et al. Proc. Natl. Acad. Sci. 2015, 8260−8265.

[5] Gu, Z.; Langer, R. S.; Anderson, D. G. et al. ACS Nano 2013, 4194−4201.


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