Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer

Hsuan Chen Liu, Daniel Davila Gonzalez, Dixita Ishani Viswanath, Robin Shae Vander Pol, Shani Zakiya Saunders, Nicola Di Trani, Yitian Xu, Junjun Zheng, Shu Hsia Chen, Corrine Ying Xuan Chua, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2206873
Pages (from-to)e2206873
JournalAdvanced Science
Volume10
Issue number9
DOIs
StatePublished - Mar 24 2023

Keywords

  • drug delivery
  • immunotherapy
  • implantable device
  • pancreatic cancer
  • sustained release
  • Carcinoma, Pancreatic Ductal/drug therapy
  • Antibodies, Monoclonal/therapeutic use
  • Tumor Microenvironment
  • CD40 Antigens
  • Animals
  • Immunotherapy
  • Mice
  • Immunosuppressive Agents/therapeutic use
  • Pancreatic Neoplasms/drug therapy

ASJC Scopus subject areas

  • General Engineering
  • General Physics and Astronomy
  • General Chemical Engineering
  • General Materials Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Medicine (miscellaneous)

Fingerprint

Dive into the research topics of 'Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer'. Together they form a unique fingerprint.

Cite this