TY - JOUR
T1 - Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer
AU - Liu, Hsuan Chen
AU - Davila Gonzalez, Daniel
AU - Viswanath, Dixita Ishani
AU - Vander Pol, Robin Shae
AU - Saunders, Shani Zakiya
AU - Di Trani, Nicola
AU - Xu, Yitian
AU - Zheng, Junjun
AU - Chen, Shu Hsia
AU - Chua, Corrine Ying Xuan
AU - Grattoni, Alessandro
N1 - Funding Information:
C.Y.X.C. and A.G. contributed equaly to this work. The authors thank Dr. Andreana L. Rivera, Yulan Ren, and Sandra Steptoe from the Research Pathology Core of Houston Methodist Research Institute, Dr. David L. Haviland from the Flow Cytometry Core of Houston Methodist Research Institute, and ImmunoMonitoring Core at Houston Methodist Research Institute. Funding support was received from the Golfers Against Cancer (A.G., C.Y.X.C., and S.‐H.C.) and the development of the nanochannel membrane was funded by NIH‐NIGMS R01GM127558 (A.G.). Additional support was received through the Frank J. and Jean Raymond Centennial Chair Endowment.
Funding Information:
C.Y.X.C. and A.G. contributed equaly to this work. The authors thank Dr. Andreana L. Rivera, Yulan Ren, and Sandra Steptoe from the Research Pathology Core of Houston Methodist Research Institute, Dr. David L. Haviland from the Flow Cytometry Core of Houston Methodist Research Institute, and ImmunoMonitoring Core at Houston Methodist Research Institute. Funding support was received from the Golfers Against Cancer (A.G., C.Y.X.C., and S.-H.C.) and the development of the nanochannel membrane was funded by NIH-NIGMS R01GM127558 (A.G.). Additional support was received through the Frank J. and Jean Raymond Centennial Chair Endowment.
Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2023/3/24
Y1 - 2023/3/24
N2 - Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold-to-hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low-dose intratumoral delivery of CD40 mAb via the nanofluidic drug-eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment-related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth inhibition in distant untreated tumors. Overall, the NDES is presented as a viable approach to penetrate the PDAC immune barrier in a minimally invasive and effective manner, for the overarching goal of transforming treatment.
AB - Agonist CD40 monoclonal antibodies (mAb) is a promising immunotherapeutic agent for cold-to-hot tumor immune microenvironment (TIME) conversion. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal cancer known as an immune desert, and therefore urgently needs more effective treatment. Conventional systemic treatment fails to effectively penetrate the characteristic dense tumor stroma. Here, it is shown that sustained low-dose intratumoral delivery of CD40 mAb via the nanofluidic drug-eluting seed (NDES) can modulate the TIME to reduce tumor burden in murine models. NDES achieves tumor reduction at a fourfold lower dosage than systemic treatment while avoiding treatment-related adverse events. Further, abscopal responses are shown where intratumoral treatment yields growth inhibition in distant untreated tumors. Overall, the NDES is presented as a viable approach to penetrate the PDAC immune barrier in a minimally invasive and effective manner, for the overarching goal of transforming treatment.
KW - drug delivery
KW - immunotherapy
KW - implantable device
KW - pancreatic cancer
KW - sustained release
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U2 - 10.1002/advs.202206873
DO - 10.1002/advs.202206873
M3 - Article
C2 - 36658712
AN - SCOPUS:85147034577
VL - 10
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
IS - 9
M1 - 2206873
ER -