An agonist antibody that blocks autoimmunity by inducing anti-inflammatory macrophages.
We have devised a method of using intracellular combinatorial libraries to select antibodies that control cell fates. Many agonist antibodies have been selected with this method, and the process appears to be limited only by the availability of a phenotypic selection system. We demonstrate the utility of this approach to discover agonist antibodies that engage an unanticipated target and regulate macrophage polarization by selective induction of anti-inflammatory M2 macrophages. This antibody was used therapeutically to block autoimmunity in a classic mouse model of spontaneous systemic lupus erythematosus.
*Department of Cell and Molecular Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Kyung Ho
KH
Han
*Department of Cell and Molecular Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Rosana
R
Gonzalez-Quintial
*Department of Cell and Molecular Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Yingjie
Y
Peng
*Department of Cell and Molecular Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Roberto
R
Baccala
*Department of Cell and Molecular Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Argyrios N
AN
Theofilopoulos
*Department of Cell and Molecular Biology and Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA rlerner@scripps.edu.
Richard A
RA
Lerner
D000818:Animals; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D057127:Single-Chain Antibodies / Q000276:immunology / Q000494:pharmacology*
D057127:Single-Chain Antibodies
CD14; CTSG; M2 macrophage; cathepsin G