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 intra-tumoral immuno-therapeutics delivery in a sustained manner. In this report, we showed progress in three tasks: 1) We investigated the bio-distribution of PDL1 antibody delivered via NDES in 4T1 and EMT triple-negative breast cancer murine models. NDES demonstrated high drug retention within the tumor with minimal systemic dissemination, compared to bolus intra-tumoral (IT) or intraperitoneal (IP) delivery approaches. IP groups showed high levels of PDL1 antibody accumulation in liver indicative of potential systemic toxicity. We further demonstrated that the addition of radiotherapy had no effect in PDL1 antibody bio-distribution. 2) The immune cell landscape associated with IP, IT and NDES drug delivery methods were examined by imaging mass cytometry. NDES delivery enhanced myeloid cell infiltration at early time points of day 3 and 7. However, our result on day 14 time point indicated that PDL1 antibody alone may be insufficient to maintain anti-tumor immune response. 3) Treatment efficacy of CD40 antibody as well as combination of CD40 and PDL1 antibodies were evaluated in EMT6 model with and without radiation treatment. IP, IT, and NDES drug delivery approaches were investigated. IP administration of combination CD40 and PDL1 antibodies achieved the highest tumor reduction whereby the addition of radiation did not improve growth inhibition. We postulate that a higher drug release rate from NDES is needed to effectively target EMT6.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1147540
Entities
People
- Alessandro Grattoni
Organizations
- Houston Methodist Research Institute