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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-02-0513.
Submitted February 20, 2002
Accepted December 31, 1969
Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX
Angela M Krackhardt, Mathias Witzens, Sabine Harig, F S Hodi, A J Zauls, Morgan Chessia, Patrick Barrett, and John G Gribben*
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Medizinische Klinik III, Haematologie, Onkologie und Transfusionsmedizin, Universitaetsklinikum Benjamin Franklin, Berlin, Germany
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
* Corresponding author; email: john_gribben{at}dfci.harvard.edu.
Chronic lymphocytic leukemia is associated with a variety of immunological disturbances. Hypogammaglobulinemia and autoimmune phenomena are both often present in this disease. In contrast, humoral or cellular antitumor responses are rarely observed. It has been previously shown that antigens detected by patients with malignant diseases can provide information regarding intracellular molecules engaged in the transformation process and can identify tumor antigens that may be useful for development of immunotherapeutic strategies. Serological identification by recombinant expression cloning (SEREX) has been demonstrated to be a useful method to detect tumor and tumor-associated antigens in a variety of malignancies. Although this approach is complicated in CLL, we used a modified SEREX approach and identified 14 antigens (KW-1 to KW-14) using this methodology. Several clones showed a restricted expression pattern in normal tissues. Moreover, distinctive expression of splice variants and aberrant gene expression in malignant tissue were detected. In this study, six antigens were detected exclusively by patients with CLL. Eight antigens were detected also by lymphoma patients. Healthy donors showed antibody responses against only three of the identified antigens. T cells with specific cytotoxicity against peptides derived from the two antigens tested could be generated from normal healthy donors. These findings demonstrate that humoral and cellular immune responses against CLL-associated antigens can be detected. Ongoing experiments investigate their potential for the development of immunotherapeutic strategies.
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