Fighting fire with fire: synthetic mini lymphocytes for cancer treatment
In this study, published in the prestigious journal Molecular Cancer, the researchers propose an innovative approach to drug delivery by taking advantage of the ability of tumor cells to evade the attack of the immune system.
A multidisciplinary team from the Biosanitary Research Institute of Granada (ibs.GRANADA), the University of Granada (UGR) and the Center for Genomic and Oncological Research (GENYO) in collaboration with the San Cecilio Clinical University Hospital of Granada, has developed a novel system for the treatment of triple negative breast cancer, one of the most aggressive and with the worst prognosis in women. These are mini immune cells formed by a synthetic nucleus wrapped with lymphocyte membranes (called biomimetic nanoparticles) obtained from cancer patients and whose results have shown a significant improvement in the treatment of this disease.
In this study, Researchers present a pioneering approach to drug delivery based on the ability of tumor cells to evade attack by the immune system. In this way, they manage to take advantage of this strength of tumors and turn it into a vulnerability that provides the opportunity to achieve personalized treatment directed toward cancer cells. To do this, this group of researchers has successfully developed biomimetic nanoparticles that act like mini synthetic lymphocytes, designed from patients with triple negative breast cancer. These nanoparticles mimic the immune system cells that tumors usually deactivate and contain a chemotherapy drug in their core. Thanks to this, these mini avatars have the ability to recognize cancer cells very specifically, thus facilitating their elimination through the chemotherapy they hide.
These mini synthetic immune cells have molecules such as PD1 on their surface, similar to those of lymphocytes deactivated by tumors. This allows them to specifically recognize cancer cells with complementary molecules. Researchers have shown that these nanoparticles firmly adhere to tumor cells with PDL1, improving the accumulation of chemotherapy in tumor tissue, increasing its effectiveness and reducing doses and side effects. Furthermore, these mini cells act in a dual manner: they administer their drug load specifically and work in a similar way to immunotherapy based on the interaction between PD1 and PDL1. This double action not only eliminates cancer cells, but also reduces the tumor's ability to deactivate the immune system, improving the tumor microenvironment. These results promise a future clinical application of synthetic mini lymphocytes for personalized cancer treatment, called personalized adoptive nanotherapy.
The therapeutic advantage of these mini lymphocytes is reinforced because they are partially formed by cells derived from the patients themselves, guaranteeing biocompatibility and absence of toxicity. Furthermore, the methodology used by the researchers does not require complex engineering techniques, facilitating its clinical application. This would not only improve the treatment of cancer patients and reduce toxic effects, but would also make its implementation in the health system simpler and cheaper than other advanced cancer therapies.
This novel study, carried out by a multidisciplinary team of scientists, is led by Dr. Sergio Granados Principal, who is co-head of the ibs.GRANADA group.Ae23-Translational and Integrative Oncology”, Full Professor of the Department of Biochemistry and Molecular Biology 2 of the University of Granada and head of the “Precision Oncology and Biomimetic Nanomedicine” group at the GENYO research center. The work has been financed by the Carlos III Health Institute, the Spanish Association Against Cancer (AECC), the Ministry of Economy, Knowledge, Business and University of the Government of Andalusia, as well as by the Doctores Galera y Requena Research Chair in cancer stem cells from the University of Granada, and the Association for the Fight against Cancer of Rota ROLUCAN.
About the research group
This group is dedicated to clinical, translational and integrative research in oncology, with the main objective of translating advances in basic research into clinical applications that improve health. Its focus on translational medicine seeks to maximize the economic and medical benefits derived from the effort in basic research. His main lines of research are Translational Oncology and Integrative Oncology.
More information about the group: https://www.ibsgranada.es/grupos-de-investigacion/ae23-oncologia-traslacional-e-integrativa/
Bibliographic reference:
Blaya-Cánovas JL, Griñán-Lisón C, Blancas I, Marchal JA, Ramírez-Tortosa C, López-Tejada A, Benabdellah K, Cortijo-Gutiérrez M, Cano-Cortés MV, Graván P, Navarro-Marchal SA, Gómez-Morales J, Delgado-Almenta V, Calahorra J, Agudo-Lera M, Sagarzazu A, Rodríguez-González CJ, Gallart-Aragón T, Eich C, Sánchez-Martín RM, Granados-Principal S. Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy. Mol Cancer. 2024 May 9;23(1):83. doi:10.1186/s12943-024-01997-x.
