Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Padler-Karavani, V.; Hurtado-Ziola, N.; Pu, M.; Yu, H.; Huang, S.; Muthana, S.; Chokhawala, H. A.; Cao, H.; Secrest, P.; Friedmann-Morvinski, D.; Singer, O.; Ghaderi, D.; Verma, I. M.; Liu, Y. T.; Messer, K.; Chen, X.; Ajit Varki; Schwab, R.
Year of Publication: 2011
Journal: Cancer Res
Volume: 71
Edition: 2011/04/21
Number: 9
Pagination: 3352-63
Date Published: May 1
Type of Article: Research Support, N.I.H., Extramural
Publication Language: eng
ISBN Number: 1538-7445 (Electronic)00
Accession Number:
Keywords: Adenocarcinoma/blood/immunology/therapy, Animals, Autoantibodies/*blood/immunology/*pharmacology, Breast Neoplasms/blood/immunology/therapy, Colonic Neoplasms/blood/immunology/therapy, Humans, Immunization, Immunoglobulin G/immunology/is, Passive/*methods
Abstract:

Human carcinomas can metabolically incorporate and present the dietary non-human sialic acid Neu5Gc, which differs from the human sialic acid N-acetylneuraminic acid (Neu5Ac) by 1 oxygen atom. Tumor-associated Neu5Gc can interact with low levels of circulating anti-Neu5Gc antibodies, thereby facilitating tumor progression via chronic inflammation in a human-like Neu5Gc-deficient mouse model. Here we show that human anti-Neu5Gc antibodies can be affinity-purified in substantial amounts from clinically approved intravenous IgG (IVIG) and used at higher concentrations to suppress growth of the same Neu5Gc-expressing tumors. Hypothesizing that this polyclonal spectrum of human anti-Neu5Gc antibodies also includes potential cancer biomarkers, we then characterize them in cancer and noncancer patients' sera, using a novel sialoglycan microarray presenting multiple Neu5Gc-glycans and control Neu5Ac-glycans. Antibodies against Neu5Gcalpha2-6GalNAcalpha1-O-Ser/Thr (GcSTn) were found to be more prominent in patients with carcinomas than with other diseases. This unusual epitope arises from dietary Neu5Gc incorporation into the carcinoma marker Sialyl-Tn, and is the first example of such a novel mechanism for biomarker generation. Finally, human serum or purified antibodies rich in anti-GcSTn-reactivity kill GcSTn-expressing human tumors via complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. Such xeno-autoantibodies and xeno-autoantigens have potential for novel diagnostics, prognostics, and therapeutics in human carcinomas.

Notes:

Cancer Res. 2011 May 1;71(9):3352-63. doi: 10.1158/0008-5472.CAN-10-4102. Epub 2011 Apr 19. 

Custom 2:

3085609

Alternate Journal: Cancer research
Author Address:

University of California at San Diego, CA, USA.

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