Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma

• Published in: Science advances Vol. 4; no. 11; p. eaau4580
• Main Authors: Stepanov, Alexey V, Markov, Oleg V, Chernikov, Ivan V, Gladkikh, Daniil V, Zhang, Hongkai, Jones, Teresa, Sen'kova, Alexandra V, Chernolovskaya, Elena L, Zenkova, Marina A, Kalinin, Roman S, Rubtsova, Maria P, Meleshko, Alexander N, Genkin, Dmitry D, Belogurov, Jr, Alexey A, Xie, Jia, Gabibov, Alexander G, Lerner, Richard A
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01-11-2018
• Subjects: Cancer; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aau4580

We report the development of a novel platform to enhance the efficacy and safety of follicular lymphoma (FL) treatment. Since lymphoma is a clonal malignancy of a diversity system, every tumor has a different antibody on its cell surface. Combinatorial autocrine-based selection is used to rapidly identify specific ligands for these B cell receptors on the surface of FL tumor cells. The selected ligands are used in a chimeric antigen receptor T cell (CAR-T) format for redirection of human cytotoxic T lymphocytes. Essentially, the format is the inverse of the usual CAR-T protocol. Instead of being a guide molecule, the antibody itself is the target. Thus, these studies raise the possibility of personalized treatment of lymphomas using a private antibody binding ligand that can be obtained in a few weeks.