Intratumorally anchored cytokine therapy
Name
Intratumorally anchored cytokine therapy.pdf
Description
Published version
Size
1.01 MB
Format
Adobe PDF
Checksum (MD5)
5b3007964602ff67e207bdc169184623
Author(s)
Wittrup, K Dane
Kaufman, Howard L
Schmidt, Michael M
Irvine, Darrell J
Date Issued
June 2, 2022
Journal
Expert Opinion on Drug Delivery
Publisher
Taylor & Francis
Citation
Wittrup, K. D., Kaufman, H. L., Schmidt, M. M., & Irvine, D. J. (2022). Intratumorally anchored cytokine therapy. Expert Opinion on Drug Delivery, 19(6), 725–732.
Version
Final published version
Abstract
INTRODUCTION: On-target, off-tumor toxicity severely limits systemic dosing of cytokines and agonist antibodies for cancer. Intratumoral administration is increasingly being explored to mitigate this problem. Full exploitation of this mode of administration must include a mechanism for sustained retention of the drug; otherwise, rapid diffusion out of the tumor eliminates any advantage.
AREAS COVERED: We focus here on strategies for anchoring immune agonists in accessible formats. Such anchoring may utilize extracellular matrix components, cell surface receptor targets, or exogenously administered particulate materials. Promising alternative strategies not reviewed here include slow release from the interior of a material depot, expression following local transfection, and conditional proteolytic activation of masked molecules.
EXPERT OPINION: An effective mechanism for tissue retention is a critical component of intratumorally anchored cytokine therapy, as leakage leads to decreased tumor drug exposure and increased systemic toxicity. Matching variable drug release kinetics with receptor-mediated cellular uptake is an intrinsic requirement for the alternative strategies mentioned above. Bioavailability of an anchored form of the administered drug is key to obviating this balancing act.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1080/17425247.2022.2084070
