TY - JOUR
T1 - Engineered implantable vaccine platform for continuous antigen-specific immunomodulation
AU - Viswanath, Dixita Ishani
AU - Liu, Hsuan Chen
AU - Capuani, Simone
AU - Vander Pol, Robin Shae
AU - Saunders, Shani Zakiya
AU - Chua, Corrine Ying Xuan
AU - Grattoni, Alessandro
N1 - Funding Information:
Funding support for this work was provided by U54CA210181 , The Nancy Owens Breast Cancer Foundation , the Houston Methodist Research Institute (HMRI) . D.I.V. received joint funding support from Texas A&M University MD/PhD Program and HMRI . The authors would like to thank Dr. Andreana Rivera and Yuelan Ren from the research pathology core of HMRI for their invaluable histopathological support. We would like to thank Dr. Michael Ittmann from Baylor College of Medicine and Dr. Andreana Rivera for histopathological scoring. Additionally, we would like to thank Dr. Jianhua “James” Gu from the electron microscopy core of HMRI for device SEM imaging. We thank the NIH Tetramer Core Facility for the provision of H–2K(b) SIINFEKL PE-labeled tetramer. The authors also thank Nathaneal Hernandez for valuable technical support, Nicola Di Trani and Jesus Paez Mayorga for useful discussions.
Funding Information:
Funding support for this work was provided by U54CA210181, The Nancy Owens Breast Cancer Foundation, the Houston Methodist Research Institute (HMRI). D.I.V. received joint funding support from Texas A&M University MD/PhD Program and HMRI. The authors would like to thank Dr. Andreana Rivera and Yuelan Ren from the research pathology core of HMRI for their invaluable histopathological support. We would like to thank Dr. Michael Ittmann from Baylor College of Medicine and Dr. Andreana Rivera for histopathological scoring. Additionally, we would like to thank Dr. Jianhua ?James? Gu from the electron microscopy core of HMRI for device SEM imaging. We thank the NIH Tetramer Core Facility for the provision of H?2K(b) SIINFEKL PE-labeled tetramer. The authors also thank Nathaneal Hernandez for valuable technical support, Nicola Di Trani and Jesus Paez Mayorga for useful discussions.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/2
Y1 - 2022/2
N2 - Cancer vaccines harness the host immune system to generate antigen-specific antitumor immunity for long-term tumor elimination with durable immunomodulation. Commonly investigated strategies reintroduce ex vivo autologous dendritic cells (DCs) but have limited clinical adoption due to difficulty in manufacturing, delivery and low clinical efficacy. To combat this, we designed the “NanoLymph”, an implantable subcutaneous device for antigen-specific antitumor immunomodulation. The NanoLymph consists of a dual-reservoir platform for sustained release of immune stimulants via a nanoporous membrane and hydrogel-encapsulated antigens for local immune cell recruitment and activation, respectively. Here, we present the development and characterization of the NanoLymph as well as efficacy validation for immunomodulation in an immunocompetent murine model. Specifically, we established the NanoLymph biocompatibility and mechanical stability. Further, we demonstrated minimally invasive transcutaneous refilling of the drug reservoir in vivo for prolonging drug release duration. Importantly, our study demonstrated that local elution of two drugs (GMCSF and Resiquimod) generates an immune stimulatory microenvironment capable of local DC recruitment and activation and generation of antigen-specific T lymphocytes within 14 days. In summary, the NanoLymph approach can achieve in situ immunomodulation, presenting a viable strategy for therapeutic cancer vaccines.
AB - Cancer vaccines harness the host immune system to generate antigen-specific antitumor immunity for long-term tumor elimination with durable immunomodulation. Commonly investigated strategies reintroduce ex vivo autologous dendritic cells (DCs) but have limited clinical adoption due to difficulty in manufacturing, delivery and low clinical efficacy. To combat this, we designed the “NanoLymph”, an implantable subcutaneous device for antigen-specific antitumor immunomodulation. The NanoLymph consists of a dual-reservoir platform for sustained release of immune stimulants via a nanoporous membrane and hydrogel-encapsulated antigens for local immune cell recruitment and activation, respectively. Here, we present the development and characterization of the NanoLymph as well as efficacy validation for immunomodulation in an immunocompetent murine model. Specifically, we established the NanoLymph biocompatibility and mechanical stability. Further, we demonstrated minimally invasive transcutaneous refilling of the drug reservoir in vivo for prolonging drug release duration. Importantly, our study demonstrated that local elution of two drugs (GMCSF and Resiquimod) generates an immune stimulatory microenvironment capable of local DC recruitment and activation and generation of antigen-specific T lymphocytes within 14 days. In summary, the NanoLymph approach can achieve in situ immunomodulation, presenting a viable strategy for therapeutic cancer vaccines.
KW - Cancer vaccine
KW - Immunomodulation
KW - In situ delivery
KW - Local controlled release
KW - Oncoimmunotherapy
KW - Subcutaneous implant
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U2 - 10.1016/j.biomaterials.2022.121374
DO - 10.1016/j.biomaterials.2022.121374
M3 - Article
C2 - 35066287
AN - SCOPUS:85123034019
VL - 281
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
M1 - 121374
ER -