Non-progressing cancer patients have persistent B cell responses expressing shared antibody paratopes that target public tumor antigens

Bibliographische Detailangaben
Veröffentlicht in:	Clinical immunology (Orlando, Fla.). - 1999. - 187(2018) vom: 15. Feb., Seite 37-45
1. Verfasser:	DeFalco, Jeff (VerfasserIn)
Weitere Verfasser:	Harbell, Michael, Manning-Bog, Amy, Baia, Gilson, Scholz, Alexander, Millare, Beatriz, Sumi, May, Zhang, Danhui, Chu, Felix, Dowd, Christine, Zuno-Mitchell, Patricia, Kim, Dongkyoon, Leung, Yvonne, Jiang, Shuwei, Tang, Xiaobin, Williamson, Kevin S, Chen, Xiaomu, Carroll, Sean M, Espiritu Santo, Gregg, Haaser, Nicole, Nguyen, Ngan, Giladi, Eldar, Minor, David, Tan, Yann Chong, Sokolove, Jeremy B, Steinman, Lawrence, Serafini, Tito A, Cavet, Guy, Greenberg, Norman M, Glanville, Jacob, Volkmuth, Wayne, Emerling, Daniel E, Robinson, William H
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2018
Zugriff auf das übergeordnete Werk:	Clinical immunology (Orlando, Fla.)
Schlagworte:	Journal Article Research Support, Non-U.S. Gov't Antibodies Antigens, Neoplasm

Beschreibung
Zusammenfassung:	Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved. There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility
Beschreibung:	Date Completed 18.03.2019 Date Revised 18.03.2019 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-7035
DOI:	10.1016/j.clim.2017.10.002