(396f) Enhanced Cancer Immunotherapy By Microneedle Patch-Assisteddelivery of Anti-PD1 Antibody

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

Yanqi Ye^a,
b, Chao Wang^{a, b}, Gabrielle
M. Hochu^a , Hasan Sadeghifar^c, Zhen Gu^{a, 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.