The macrophage-drug conjugate (MDC) as a "Trojan horse" approach in cancer therapy.

Unsatisfactory response of tumors to chemotherapy is mainly related to impaired diffusion of the anticancer drug because of decreased drug uptake due to poor vasculature. Moreover, the drug is not able to penetrate the most hypoxic sites. Cells from these “untreated” sites are responsible for relapse and metastasis. However, these avascular regions attract macrophages that migrate even to areas far away from blood vessels. Therefore, they might constitute a unique delivery system of drug-containing particles to these parts of the tumor mass. A promising example of such particles that could be used is ferritins, whose caged architecture allows for efficient drug encapsulation and whose uptake from macrophage cells has been well demonstrated. Macrophages are also able to specifically and actively transfer these taken-up ferritins (loaded with the anticancer drugs) to cancer cells. This is the new mechanism discovered by our team and named TRAIN (TRAnsfer of Iron-binding proteiN). Thus, there is a possibility to use macrophages to deliver ferritin-encapsulated compounds directly to the tumor cells (MDC technology—Macrophage-Drug Conjugate). This is a completely new and modern approach to anticancer therapy and drug delivery. As such, we expect to be able to precisely administer drugs to the tumor site (even to the hypoxic regions), decreasing side effects of anticancer therapy. Acknowledgments: This research is founded by the European Research Council, Starting Grant McHAP: 715048. The dissemination of the project is founded by the KNOW (Leading National Research Centre), Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015. Citation Format: Bartlomiej Taciak, Maciej Bialasek, Paulina Kucharzewska-Siembieda, Łukasz Kiraga, Aleksandra Szulc, Emilia Gorka, Malgorzata Kubiak, Zofia Pilch, Katarzyna Tonecka, Zuzanna Sas, Agata Braniewska, Łukasz Cheda, Zbigniew Rogulski, Michal Godlewski, Alberto Boffi, Tomasz Rygiel, Magdalena Krol. The macrophage-drug conjugate (MDC) as a “Trojan horse” approach in cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B24.