Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.

Abstract

Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.

• Authors: Amy E Gilbert, Panagiotis Karagiannis, Tihomir Dodev, Alexander Koers, Katie Lacy, Debra H Josephs, Pooja Takhar, Jenny L C Geh, Ciaran Healy, Mark Harries, Katharine M Acland, Sarah M Rudman, Rebecca L Beavil, Philip J Blower, Andrew J Beavil, Hannah J Gould, James Spicer, Frank O Nestle, Sophia N Karagiannis
• Journal: PloS one (PLoS One) Vol. 6 Issue 4 Pg. e19330 (Apr 29 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21559411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neoplasm
• Immunoglobulin G

Topics

• Antibodies, Monoclonal (chemistry)
• Antibodies, Neoplasm (chemistry)
• B-Lymphocytes (immunology)
• Case-Control Studies
• Cell Line
• Cell Line, Tumor
• Cohort Studies
• Disease Progression
• Enzyme-Linked Immunosorbent Assay (methods)
• Fibroblasts (metabolism)
• Humans
• Immune System
• Immunoglobulin G (blood, chemistry)
• Immunohistochemistry (methods)
• Melanoma (blood, immunology, therapy)
• Time Factors