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

Vered Padler-Karavani, Nancy Hurtado-Ziola, Minya Pu, Hai Yu, Shengshu Huang, Saddam Muthana, Harshal A. Chokhawala, Hongzhi Cao, Patrick Secrest, Dinorah Friedmann-Morvinski, Oded Singer, Darius Ghaderi, Inder M. Verma, Yu Tsueng Liu, Karen Messer, Xi Chen, Ajit Varki, Richard Schwab

Research output: Contribution to journalArticle

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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 Neu5Gca2α6GalNAcα1-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 complementdependent cytotoxicity or antibody-dependent cellular cytotoxicity. Such xeno-autoantibodies and xenoautoantigens have potential for novel diagnostics, prognostics, and therapeutics in human carcinomas.

Original languageEnglish (US)
Pages (from-to)3352-3363
Number of pages12
JournalCancer Research
Volume71
Issue number9
DOIs
StatePublished - May 1 2011

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N-Acetylneuraminic Acid
Autoantibodies
Biomarkers
Serum
Neoplasms
Carcinoma
Anti-Idiotypic Antibodies
Polysaccharides
Antibodies
Tumor Biomarkers
Epitopes
Immunoglobulin G
Oxygen
Inflammation
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Padler-Karavani, V., Hurtado-Ziola, N., Pu, M., Yu, H., Huang, S., Muthana, S., ... Schwab, R. (2011). Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. Cancer Research, 71(9), 3352-3363. https://doi.org/10.1158/0008-5472.CAN-10-4102

Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. / Padler-Karavani, Vered; Hurtado-Ziola, Nancy; Pu, Minya; Yu, Hai; Huang, Shengshu; Muthana, Saddam; Chokhawala, Harshal A.; Cao, Hongzhi; Secrest, Patrick; Friedmann-Morvinski, Dinorah; Singer, Oded; Ghaderi, Darius; Verma, Inder M.; Liu, Yu Tsueng; Messer, Karen; Chen, Xi; Varki, Ajit; Schwab, Richard.

In: Cancer Research, Vol. 71, No. 9, 01.05.2011, p. 3352-3363.

Research output: Contribution to journalArticle

Padler-Karavani, V, Hurtado-Ziola, N, Pu, M, Yu, H, Huang, S, Muthana, S, Chokhawala, HA, Cao, H, Secrest, P, Friedmann-Morvinski, D, Singer, O, Ghaderi, D, Verma, IM, Liu, YT, Messer, K, Chen, X, Varki, A & Schwab, R 2011, 'Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer', Cancer Research, vol. 71, no. 9, pp. 3352-3363. https://doi.org/10.1158/0008-5472.CAN-10-4102
Padler-Karavani, Vered ; Hurtado-Ziola, Nancy ; Pu, Minya ; Yu, Hai ; Huang, Shengshu ; Muthana, Saddam ; Chokhawala, Harshal A. ; Cao, Hongzhi ; Secrest, Patrick ; Friedmann-Morvinski, Dinorah ; Singer, Oded ; Ghaderi, Darius ; Verma, Inder M. ; Liu, Yu Tsueng ; Messer, Karen ; Chen, Xi ; Varki, Ajit ; Schwab, Richard. / Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. In: Cancer Research. 2011 ; Vol. 71, No. 9. pp. 3352-3363.
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