Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX.
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.
Krackhardt
Angela M
AM
Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Witzens
Mathias
M
Harig
Sabine
S
Hodi
F Stephen
FS
Zauls
A Jason
AJ
Chessia
Morgan
M
Barrett
Patrick
P
Gribben
John G
JG
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies; D016022:Case-Control Studies; D003001:Cloning, Molecular; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019151:Peptide Library; D016415:Sequence Alignment; D014018:Tissue Distribution
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D019151:Peptide Library