(1) DeFalco J (2) Harbell M (3) Manning-Bog A (4) Baia G (5) Scholz A (6) Millare B (7) Sumi M (8) Zhang D (9) Chu F (10) Dowd C (11) Zuno-Mitchell P (12) Kim D (13) Leung Y (14) Jiang S (15) Tang X (16) Williamson KS (17) Chen X (18) Carroll SM (19) Santo GE (20) Haaser N (21) Nguyen N (22) Giladi E (23) Minor D (24) Tan YC (25) Sokolove JB (26) Steinman L (27) Serafini TA (28) Cavet G (29) Greenberg NM (30) Glanville J (31) Volkmuth W (32) Emerling DE (33) Robinson WH

Clinical immunology

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.

Author Info: (1) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (2) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (3) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA

Author Info: (1) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (2) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (3) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (4) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (5) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (6) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (7) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (8) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (9) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (10) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (11) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (12) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (13) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (14) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (15) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (16) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (17) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (18) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (19) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (20) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (21) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (22) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (23) California Pacific Medical Center, 2100 Webster St., Suite 326, San Francisco, CA 94115, USA. (24) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA; Division of Immunology and Rheumatology, Stanford University, 269 Campus Dr., Stanford, CA 94063, USA. (25) Division of Immunology and Rheumatology, Stanford University, 269 Campus Dr., Stanford, CA 94063, USA. (26) Department of Neurology and Neurological Sciences and Pediatrics, Stanford University, 279 Campus Dr., Stanford, CA 94305, USA. (27) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (28) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (29) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (30) Department of Microbiology and Immunology, Stanford University, 279 Campus Dr., Stanford, CA 94305, USA. (31) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. (32) Atreca, Inc., 500 Saginaw Dr., Redwood City, CA 94305, USA. Electronic address: demerling@atreca.com. (33) Division of Immunology and Rheumatology, Stanford University, 269 Campus Dr., Stanford, CA 94063, USA. Electronic address: w.robinson@stanford.edu.

Citation: Clin Immunol 2017 Oct 11 Epub10/11/2017

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/29031828

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