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

Alexey V. Stepanov, Oleg V. Markov, Ivan V. Chernikov, Daniil V. Gladkikh, Hongkai Zhang, Teresa Jones, Alexandra V. Sen'Kova, Elena L. Chernolovskaya, Marina A. Zenkova, Roman S. Kalinin, Maria P. Rubtsova, Alexander N. Meleshko, Dmitry D. Genkin, Alexey A. Belogurov, Jia Xie, Alexander G. Gabibov, Richard A. Lerner

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Article numbereaau4580
JournalScience Advances
Issue number11
Publication statusPublished - 14 Nov 2018
Externally publishedYes


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