Micrograph showing a breast cancer. / Wikipedia
A work, led by the Autonoma University of Madrid and the University of Santiago de Compostela, has demonstrated the effectiveness of the first nanotherapy based on the use of unmodified antibodies directed against intracellular oncoproteins. The results represent a milestone for oncological nanomedicine and opens up new possibilities for the treatment of patients with aggressive breast cancer.
Researchers from the Autonoma University of Madrid (UAM) belonging to CIBERONC and IdiPAZ, in collaboration with the University of Santiago de Compostela (USC), the MD Anderson Foundation of Madrid (FMDA) have managed for the first time to combine the use of nanovehicles (capsules) of microscopic size to enter the tumor cells) with a therapeutic antibody directed against an intracellular protein.
This new treatment, described in the journal of Clinical Cancer Research, focused on the oncoprotein Gasdermina-B (GSDMB), since previous studies carried out by the same group at the UAM had shown that this molecule promotes aggressive behavior and resistance. to standard oncological treatments in breast tumors.
“One of the objectives of our research group is precisely the design of specific therapies that can reverse drug resistance and reduce the therapeutic failure of cancer patients,” says Gema Moreno-Bueno, director of the team of researchers at the UAM.
This team has developed a specific antibody against this oncoprotein. The antibody, bound to nanoparticles designed by the team led by María José Alonso at USC, was able to enter into tumor cells to effectively reduce tumor size and metastasis in various preclinical models, without apparent toxicity in healthy tissues.
“These results confirm for the first time the role of GSDMB as a new therapeutic target in cancer and expand the use of nanomedicine in the treatment of cancer,” says Angela Molina-Crespo, researcher at UAM and first author of the work.
Precision oncological nanomedicine
One of the objectives of current oncology is the development of new treatments that are more specific, effective and have fewer side effects. For this it is essential to identify new biomarkers that are altered in tumor cells and that could become potential therapeutic targets for the development of specific therapies. These could be treated with modern technological approaches such as nanomedicine.
In this sense, the generation of drugs directed at the tumor cell, as the basis of precision medicine, has been driven by the use of therapeutic antibodies against proteins important for tumor development. However, until now, these antibodies were mainly directed against proteins located outside the tumor cells, limiting their applicability in oncology.
Molina-Crespo A, Cadete A, Sarrio D, Gamez-Chiachio M, Martinez L, Chao K, Olivera A, Gonella A, Diaz E, Palacios J, Dhal PK, Besev M, Rodriguez-Serrano M, García-Bermejo ML, Triviño JC, Cano A, Garcia-Fuentes M, Herzberg O, Torres D, Alonso MJ, Moreno-Bueno G. “Intracellular delivery of an antibody targeting Gasdermin-B reduces HER2 breast cancer aggressiveness”. Clin Cancer Res. 2019 May 7. pii: clincanres.2381.2018. doi: 10.1158/1078-0432.CCR-18-2381. IF: 10.199
Sources: UAM y SINC