Co-delivery of dendritic cell vaccine and anti-PD-1 antibody with cryomicroneedles for combinational immunotherapy

Hao Chang; Xueyu Wen; Zhiming Li; Zhixin Ling; Yanting Zheng; Chenjie Xu

doi:10.1002/btm2.10457

Co-delivery of dendritic cell vaccine and anti-PD-1 antibody with cryomicroneedles for combinational immunotherapy

Hao Chang^*, Xueyu Wen, Zhiming Li, Zhixin Ling, Yanting Zheng, Chenjie Xu^*

^*Corresponding author for this work

Department of Biomedical Engineering

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

29 Citations (Scopus)

40 Downloads (CityUHK Scholars)

Abstract

Combinational immunotherapy of dendritic cell (DC) vaccines and anti-programmed cell death protein 1 antibodies (aPD1) has been regarded as a promising strategy for cancer treatment because it not only induces tumor-specific T cell immune responses, but also prevents failure of T cell functions by the immune suppressive milieu of tumors. Microneedles have emerged as an innovative platform for efficient transdermal immunotherapies. However, co-delivery of DC vaccines and aPD1 via microneedles has not been studied since conventional microneedle platforms are unsuitable for fragile therapeutics like living cells and antibodies. This study employs our newly invented cryomicroneedles (cryoMNs) to co-deliver DC vaccines and aPD1 for the combinational immunotherapy. CryoMNs are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended DCs and aPD1, which are further integrated with a homemade handle for convenient application. The viability of DCs in cryoMNs remains above 85%. CryoMNs are mechanically strong enough to insert into porcine and mouse skin, successfully releasing DCs and aPD1 inside skin tissue after melting. Co-delivery of ovalbumin (OVA)-pulsed DCs (OVA-DCs) and aPD1 via cryoMNs induced higher antigen-specific cellular immune responses compared with the mono-delivery of OVA-DCs or aPD1. Finally, administration with cryoMNs co-encapsulated with OVA-DCs and aPD1 increases the infiltration of effector T cells in the tumor, resulting in stronger anti-tumor therapeutic efficacy in both prophylactic and therapeutic melanoma models compared with administration with cryoMNs loaded with OVA-DCs or aPD1. This study demonstrates the great potential of cryoMNs as a co-delivery system of therapeutic cells and biomacromolecules for combinational therapies. © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

Original language	English
Article number	e10457
Journal	Bioengineering and Translational Medicine
Volume	8
Issue number	5
Online published	27 Nov 2022
DOIs	https://doi.org/10.1002/btm2.10457
Publication status	Published - Sept 2023

Funding

Hao Chang acknowledges the financial support from the National Natural Science Foundation of China (82202329), startup funding (2021QD08-1, 2021QD08-2) supported by the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, and a research grant from Medcraft Biotech. Inc. (2022HX01). Chenjie Xu appreciates the support by Start-up Grant for New Faculty (9610472) and Strategic Interdisciplinary Research Grant (7020029) from City University of Hong Kong, General Research Fund (GRF) grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region China (CityU 100168), and the Mainland/Hong Kong Joint Research Scheme sponsored by the RGC Hong Kong and the National Natural Science Foundation of China (N_CityU118/20).

Research Keywords

anti-PD-1
cancer immunotherapy
cryomicroneedles
dendritic cells
transdermal delivery

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

RGC Funding Information

RGC-funded

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access Output

10.1002/btm2.10457

126723278.pdfFinal Published version, 3.35 MBLicence: CC BY

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

@article{9f7db889731d48c791f40effc858a7d7,

title = "Co-delivery of dendritic cell vaccine and anti-PD-1 antibody with cryomicroneedles for combinational immunotherapy",

abstract = "Combinational immunotherapy of dendritic cell (DC) vaccines and anti-programmed cell death protein 1 antibodies (aPD1) has been regarded as a promising strategy for cancer treatment because it not only induces tumor-specific T cell immune responses, but also prevents failure of T cell functions by the immune suppressive milieu of tumors. Microneedles have emerged as an innovative platform for efficient transdermal immunotherapies. However, co-delivery of DC vaccines and aPD1 via microneedles has not been studied since conventional microneedle platforms are unsuitable for fragile therapeutics like living cells and antibodies. This study employs our newly invented cryomicroneedles (cryoMNs) to co-deliver DC vaccines and aPD1 for the combinational immunotherapy. CryoMNs are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended DCs and aPD1, which are further integrated with a homemade handle for convenient application. The viability of DCs in cryoMNs remains above 85%. CryoMNs are mechanically strong enough to insert into porcine and mouse skin, successfully releasing DCs and aPD1 inside skin tissue after melting. Co-delivery of ovalbumin (OVA)-pulsed DCs (OVA-DCs) and aPD1 via cryoMNs induced higher antigen-specific cellular immune responses compared with the mono-delivery of OVA-DCs or aPD1. Finally, administration with cryoMNs co-encapsulated with OVA-DCs and aPD1 increases the infiltration of effector T cells in the tumor, resulting in stronger anti-tumor therapeutic efficacy in both prophylactic and therapeutic melanoma models compared with administration with cryoMNs loaded with OVA-DCs or aPD1. This study demonstrates the great potential of cryoMNs as a co-delivery system of therapeutic cells and biomacromolecules for combinational therapies. {\textcopyright} 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.",

keywords = "anti-PD-1, cancer immunotherapy, cryomicroneedles, dendritic cells, transdermal delivery",

author = "Hao Chang and Xueyu Wen and Zhiming Li and Zhixin Ling and Yanting Zheng and Chenjie Xu",

year = "2023",

month = sep,

doi = "10.1002/btm2.10457",

language = "English",

volume = "8",

number = "5",

}

TY - JOUR

T1 - Co-delivery of dendritic cell vaccine and anti-PD-1 antibody with cryomicroneedles for combinational immunotherapy

AU - Chang, Hao

AU - Wen, Xueyu

AU - Li, Zhiming

AU - Ling, Zhixin

AU - Zheng, Yanting

AU - Xu, Chenjie

PY - 2023/9

Y1 - 2023/9

N2 - Combinational immunotherapy of dendritic cell (DC) vaccines and anti-programmed cell death protein 1 antibodies (aPD1) has been regarded as a promising strategy for cancer treatment because it not only induces tumor-specific T cell immune responses, but also prevents failure of T cell functions by the immune suppressive milieu of tumors. Microneedles have emerged as an innovative platform for efficient transdermal immunotherapies. However, co-delivery of DC vaccines and aPD1 via microneedles has not been studied since conventional microneedle platforms are unsuitable for fragile therapeutics like living cells and antibodies. This study employs our newly invented cryomicroneedles (cryoMNs) to co-deliver DC vaccines and aPD1 for the combinational immunotherapy. CryoMNs are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended DCs and aPD1, which are further integrated with a homemade handle for convenient application. The viability of DCs in cryoMNs remains above 85%. CryoMNs are mechanically strong enough to insert into porcine and mouse skin, successfully releasing DCs and aPD1 inside skin tissue after melting. Co-delivery of ovalbumin (OVA)-pulsed DCs (OVA-DCs) and aPD1 via cryoMNs induced higher antigen-specific cellular immune responses compared with the mono-delivery of OVA-DCs or aPD1. Finally, administration with cryoMNs co-encapsulated with OVA-DCs and aPD1 increases the infiltration of effector T cells in the tumor, resulting in stronger anti-tumor therapeutic efficacy in both prophylactic and therapeutic melanoma models compared with administration with cryoMNs loaded with OVA-DCs or aPD1. This study demonstrates the great potential of cryoMNs as a co-delivery system of therapeutic cells and biomacromolecules for combinational therapies. © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

AB - Combinational immunotherapy of dendritic cell (DC) vaccines and anti-programmed cell death protein 1 antibodies (aPD1) has been regarded as a promising strategy for cancer treatment because it not only induces tumor-specific T cell immune responses, but also prevents failure of T cell functions by the immune suppressive milieu of tumors. Microneedles have emerged as an innovative platform for efficient transdermal immunotherapies. However, co-delivery of DC vaccines and aPD1 via microneedles has not been studied since conventional microneedle platforms are unsuitable for fragile therapeutics like living cells and antibodies. This study employs our newly invented cryomicroneedles (cryoMNs) to co-deliver DC vaccines and aPD1 for the combinational immunotherapy. CryoMNs are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended DCs and aPD1, which are further integrated with a homemade handle for convenient application. The viability of DCs in cryoMNs remains above 85%. CryoMNs are mechanically strong enough to insert into porcine and mouse skin, successfully releasing DCs and aPD1 inside skin tissue after melting. Co-delivery of ovalbumin (OVA)-pulsed DCs (OVA-DCs) and aPD1 via cryoMNs induced higher antigen-specific cellular immune responses compared with the mono-delivery of OVA-DCs or aPD1. Finally, administration with cryoMNs co-encapsulated with OVA-DCs and aPD1 increases the infiltration of effector T cells in the tumor, resulting in stronger anti-tumor therapeutic efficacy in both prophylactic and therapeutic melanoma models compared with administration with cryoMNs loaded with OVA-DCs or aPD1. This study demonstrates the great potential of cryoMNs as a co-delivery system of therapeutic cells and biomacromolecules for combinational therapies. © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.

KW - anti-PD-1

KW - cancer immunotherapy

KW - cryomicroneedles

KW - dendritic cells

KW - transdermal delivery

UR - http://www.scopus.com/inward/record.url?scp=85143425124&partnerID=8YFLogxK

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85143425124&origin=recordpage

U2 - 10.1002/btm2.10457

DO - 10.1002/btm2.10457

M3 - RGC 21 - Publication in refereed journal

C2 - 37693072

SN - 2380-6761

VL - 8

JO - Bioengineering and Translational Medicine

JF - Bioengineering and Translational Medicine

IS - 5

M1 - e10457

ER -

Co-delivery of dendritic cell vaccine and anti-PD-1 antibody with cryomicroneedles for combinational immunotherapy

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

UN SDGs

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

NSFC: Nanometallic Conductive Composite-hydrogel Core-shell Microneedle Skin Patch for Real-time Monitoring Physiological Signals

Cite this

Co-delivery of dendritic cell vaccine and anti-PD-1 antibody with cryomicroneedles for combinational immunotherapy

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

UN SDGs

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

NSFC: Nanometallic Conductive Composite-hydrogel Core-shell Microneedle Skin Patch for Real-time Monitoring Physiological Signals

Cite this