Originally published as JCO Early Release 10.1200/JCO.2006.05.9311 on August 14 2006

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T-Cell Immunity to the Folate Receptor Alpha Is Prevalent in Women With Breast or Ovarian Cancer

Keith L. Knutson, Christopher J. Krco, Courtney L. Erskine, Karin Goodman, Linda E. Kelemen, Peter J. Wettstein, Philip S. Low, Lynn C. Hartmann, Kimberly R. Kalli

From the Departments of Immunology, Oncology, Health Sciences Research and Surgery, Mayo Clinic College of Medicine, Rochester MN; and the Department of Chemistry, Purdue University, West Lafayette, IN.

Address reprint requests to Keith L. Knutson, PhD, Mayo Clinic, Department of Immunology, Guggenheim 3, 200 First St. SW, Rochester, MN 55905; e-mail: knutson.keith{at}mayo.edu

Purpose: Studies have demonstrated that the generation of immunity to tumor antigens is associated with improved prognosis for many cancers. A candidate antigen is the folate receptor alpha (FR), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FR immunity.

Methods: Using a CD4⁺ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FR, and tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and 18 healthy donors using enzyme-linked immunospot analysis.

Results: Fourteen peptides were predicted, seven each from the carboxy- and amino-terminus halves of the protein. More than 70% of patients demonstrated immunity to at least one FR peptide. Patients responded to an average of 3 ± 0.5 peptides, whereas healthy donors responded to 1 ± 0.4 peptides (P = .004). Five peptides were recognized by more than 25% of patients. Responses to three peptides were higher (P < .05) in patients than in healthy donors, suggesting augmented immunity. Compared with healthy individuals, patients developed higher immunity to the amino-terminus half of the receptor (P = .03). There was no difference between each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5). Lastly, patients demonstrated elevated levels of FR antibodies consistent with a coordinated immune response.

Conclusion: These findings demonstrate that the FR is a target of the immune system in breast and ovarian cancer patients. Understanding which antigens are targeted by the immune system may be important for prognosis or immune-based therapies.

published online ahead of print at www.jco.org on August 14, 2006.

Supported by Commonwealth Foundation for Cancer Research and National Institutes of Health/National Cancer Institute award, K01CA100764.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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