High activity and low toxicity of a novel CD71-targeting nanotherapeutic named The-0504 on preclinical models of several human aggressive tumors
Autor: | Elisabetta Falvo, Federico Boschi, Verena Damiani, Veronica Morea, Michele Milella, Gianluca Sala, Giulio Fracasso, Pierpaolo Ceci, Giamaica Conti, Katia Messana, Patrizio Giacomini, Vincenzo De Laurenzi |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Tumor targeted therapy Human ferritin medicine.medical_treatment Mice Nude Preclinical studies Transferrin receptor lcsh:RC254-282 Flow cytometry Mice 03 medical and health sciences Gastrointestinal cancer 0302 clinical medicine Breast cancer Antigens CD In vivo Cell Line Tumor Neoplasms Receptors Transferrin Biomarkers Tumor medicine Animals Humans Transferrin receptor 1 (CD71) Chemotherapy medicine.diagnostic_test business.industry Research Cancer medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Nanostructures Rats 030104 developmental biology Oncology 030220 oncology & carcinogenesis Ferritins Cancer research Immunohistochemistry Female business |
Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-14 (2021) Journal of experimental & clinical cancer research (Online) 40 (2021). doi:10.1186/s13046-021-01851-8 info:cnr-pdr/source/autori:Falvo, Elisabetta; Damiani, Verena; Conti, Giamaica; Boschi, Federico; Messana, Katia; Giacomini, Patrizio; Milella, Michele; De Laurenzi, Vincenzo; Morea, Veronica; Sala, Gianluca; Fracasso, Giulio; Ceci, Pierpaolo/titolo:High activity and low toxicity of a novel CD71-targeting nanotherapeutic named The-0504 on preclinical models of several human aggressive tumors/doi:10.1186%2Fs13046-021-01851-8/rivista:Journal of experimental & clinical cancer research (Online)/anno:2021/pagina_da:/pagina_a:/intervallo_pagine:/volume:40 Journal of Experimental & Clinical Cancer Research : CR |
ISSN: | 1756-9966 |
Popis: | Background Ferritin receptor (CD71) is an example of a very attractive cancer target, since it is highly expressed in virtually all tumor types, including metastatic loci. However, this target can be considered to be inaccessible to conventional target therapies, due to its presence in many healthy tissues. Here, we describe the preclinical evaluation of a tumor proteases-activatable human ferritin (HFt)-based drug carrier (The-0504) that is able to selectively deliver the wide-spectrum topoisomerase I inhibitor Genz-644282 to CD71-expressing tumors, preventing the limiting toxic effects associated with CD71-targeting therapies. Methods CD71 expression was evaluated using flow cytometry and immunohistochemistry techniques. The-0504 antiproliferative activity towards several cancer cell lines was assessed in vitro. The-0504 antitumor efficacy and survival benefit were evaluated in different human tumors, which had been grown either as xenografts or patient-derived xenografts in mice. The-0504 toxicology profile was investigated in multiple-cycle repeat-dose study in rodents. Results In vitro studies indicate that The-0504 is highly specific for CD71 expressing cells, and that there is a relationship between CD71 levels and The-0504 anticancer activity. In vivo treatments with The-0504 showed a remarkable efficacy, eradicating several human tumors of very diverse and aggressive histotypes, such as pancreas, liver and colorectal carcinomas, and triple-negative breast cancer. Conclusions Durable disease-free survival, persistent antitumor responses after discontinuation of treatment and favorable toxicology profile make The-0504 an ideal candidate for clinical development as a novel, CD71-targeted, low-toxicity alternative to chemotherapy. |
Databáze: | OpenAIRE |
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