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CD137 (4-1BB) receptor mechanism identified that elicits immune response to tumors

Researchers at Cima University of Navarra confirm that cIAPs proteins play a crucial role in the activation and function of lymphocytes through the CD137 receptor and promote their antitumor effect.

/Javier González Vaz and Ignacio Melero, from Cima University of Navarra.

11 | 09 | 2023

A research conducted by scientists at Cima University of Navarra, part of the Cancer Center Clínica Universidad de Navarra, has identified a mechanism of the CD137 (4-1BB) receptor that triggers the immune response to tumors.

The CD-137 (4-1BB) receptor has been shown to be effective in stimulating the function of lymphocytes capable of recognizing and destroying tumors. To exploit its activity, antibodies from laboratory capable of interacting with this receptor and determining that it functions by transmitting signals into the cells of the immune system are used.

Chimeric antigen receptors (CARs) approved for clinical use incorporate the sequence capable of transmitting signals from the CD137 receptor. "Our work has discovered that the function of cIAP proteins is necessary for the correct signal transduction of CARs that are currently used in the treatment of various hematological malignancies such as leukemias, lymphomas and myeloma," explains Dr. Ignacio Melero, co-director of the Immunology and Immunotherapy Program at Cima University of Navarra and director of work.

The study, carried out at partnership with scientists from high school de Investigaciones Biomédicas Alberto Sols and CNB-CSIC, has been published in the latest issue of the scientific journal Science Advances.

Advances in proteomics

According to Javier Gonzalez Vaz, first author of work, "proteomics results on new signaling molecules physically associated with CD137 (4-1BB) are giving rise to new programs of study that will undoubtedly help to clarify and improve the therapeutic effect of CARs approved for clinical use".

The published work is in the context of exploiting the CD137 receptor for cancer immunotherapy. Specifically, a recent article published in Cancer Discovery, the group of Cima reviewed major advances on the use of CD137 (4-1BB) in cancer immunotherapy, on the occasion of the 25th anniversary of the first successful experiments in tumor-bearing mice initiated by Dr. Melero in Seattle in 1996.

The study was carried out thanks to funding from the Ministry of Science and Innovation, the Government of Navarra (through the LINTERNA Strategic project ), the BBVA Foundation, the FERO Foundation, the La Caixa Foundation and the association Española Contra el Cáncer, among other public and private institutions.

reference letter bibliographic

Science Advances CD137 (4-1BB) requires physically associated cIAPs for signal transduction and antitumor effects