Transforming Triple-Negative Breast Cancer Treatment Through Intratumoral Immunotherapy via Nanofluidic Drug-Eluting Seed
Abstract
The research addresses the overarching challenge to "revolutionize treatment regimens with ones that are more effective, less toxic, and impact survival." Our approach is to utilize the nanofluidic drug-eluting seed (NDES) for intratumoral immunotherapeutics delivery in a sustained manner. In this report, we showed three major tasks: 1) In addition to determining the biodistribution of PDL1 antibody in the 4T1 and EMT6 via NDES, bolus intratumoral (IT), and intraperitoneal (IP) delivery approach, we performed an extensive investigation of tumor properties, including tumor density, vasculature formation, molecules diffusion coefficient and the percentage of collagen in 4T1 and EMT6 models. We learned that EMT6 tumors showed higher density compared to 4T1 tumors through a series of evaluations. 2) CyTOF analysis revealed the default NDES release rate was insufficient to treat EMT6 tumors. We increased the release rate of NDES. The tumor growth of EMT6 with increased NDES release rate showed effective combinational treatment of radiation therapy and PDL1+CD40 mAbs. Tumor immune microenvironment analysis with optimized NDES rate is currently in progress. 3) We utilized the 4T1 bilateral murine tumor model to assess the systemic treatment effect. 4T1 tumor model is highly metastatic and aggressive, the treatment showed reduced tumor growth on the treated tumor, but no effect on the untreated tumor. An enhanced release of NDES may be required for the bilateral tumor model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1191179
Entities
People
- Alessandro Grattoni
Organizations
- Houston Methodist Research Institute