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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-02-0513.
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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2123-2131
IMMUNOBIOLOGY
Identification of tumor-associated antigens in chronic
lymphocytic leukemia by SEREX
Angela M. Krackhardt,
Mathias Witzens,
Sabine Harig,
F. Stephen Hodi,
A. Jason Zauls,
Morgan Chessia,
Patrick Barrett, and
John G. Gribben
From the Department of Adult Oncology, Dana Farber
Cancer Institute; and Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School; both of Boston, MA; and Medizinische
Klinik III, Hämatologie, Onkologie und Transfusionsmedizin,
Universitätsklinikum Benjamin Franklin, Berlin, Germany.
Chronic lymphocytic leukemia (CLL) is associated with a variety of
immunologic 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 in 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.
Serologic 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, 6 antigens were detected exclusively in patients with CLL. Eight
antigens were detected also in lymphoma patients. Healthy donors showed
antibody responses against only 3 of the identified antigens. T cells
with specific cytotoxicity against peptides derived from the 2 antigens
tested could be generated from 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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