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

Abstract

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.

• Authors: 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 Jr, Jia Xie, Alexander G Gabibov, Richard A Lerner
• Journal: Science advances (Sci Adv) Vol. 4 Issue 11 Pg. eaau4580 (11 2018) ISSN: 2375-2548 [Electronic] United States
• PMID: 30443597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Peptide Fragments
• Receptors, Antigen, B-Cell
• Receptors, Antigen, T-Cell

Topics

• Animals
• Autocrine Communication
• Female
• Humans
• Ligands
• Lymphoma, B-Cell (immunology, metabolism, therapy)
• Mice, Inbred NOD
• Mice, SCID
• Peptide Fragments (immunology, metabolism)
• Receptors, Antigen, B-Cell (immunology, metabolism)
• Receptors, Antigen, T-Cell (immunology, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays