Quantification of recombinant immunotoxin delivery to solid tumors allows for direct comparison of in vivo and in vitro results.

ABSTRACT: Solid tumors present challenges for delivery of protein therapeutics; current methods cannot quantify the functional effects of these agents. RG7787 (anti-mesothelin recombinant immunotoxin) is highly cytotoxic to pancreatic cancer cell lines, but with limited activity in vivo. To investigate this discrepancy, we developed a flow cytometry method to quantify the amount of RG7787 internalized per cell in tumors and used it to analyze tumor responses by determining the number of molecules of RG7787 internalized per cell in vivo and comparing it to that needed to kill cells in vitro. At a maximum tolerated dose of 7.5 mg/kg, tumor cells in vivo internalized a wide range of RG7787 with the average amount equivalent to the amount that induced growth arrest in vitro. However, 20% of cells accumu

SUBMITTER: Mason-Osann E 

PROVIDER: S-EPMC4482048 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature