Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies.
Wilms tumor gene WT1 is expressed at high levels in hematopoietic malignancies, such as leukemias and myelodysplastic syndromes (MDS), and in various kinds of solid tumors, including lung cancer, and it exerts an oncogenic function in these malignancies. IgM and IgG WT1 antibodies were measured by means of dot blot assay in 73 patients with hematopoietic malignancies (16 acute myeloid leukemia [AML], 11 acute lymphoid leukemia [ALL], 13 chronic myeloid leukemia [CML], and 33 MDS) and 43 healthy volunteers. Immunoglobulin IgM, IgG, and IgM+IgG WT1 antibodies were detected in 40 (54.8%), 40 (54.8%), and 24 (32.8%), respectively, of the 73 patients with hematopoietic malignancies, whereas 7 (16.2%), 2 (4.7%), and none of the 43 healthy volunteers had IgM, IgG, or IgM+IgG WT1 antibodies, respectively. Furthermore, immunoglobulin isotype class switching of WT1 antibodies from IgM to IgG occurred in conjunction with disease progression from refractory anemia (RA) to RA with excess of blasts (RAEB), and further to RAEB in transformation (RAEB-t) in MDS patients. These results showed that humoral immune responses against the WT1 protein could be elicited in patients with WT1-expressing hematopoietic malignancies, and they suggested that the helper T-cell responses needed to induce humoral immune responses and immunoglobulin isotype class switching from IgM to IgG were also generated in these patients. Our findings may provide new insight into the rationale for elicitation of cytotoxic T-cell responses against the WT1 protein in cancer immunotherapy using the WT1 vaccine.
Elisseeva
Olga A
OA
Department of Radiation Biology, Osaka University Medical School, Japan.
Oka
Yoshihiro
Y
Tsuboi
Akihiro
A
Ogata
Kiyoyuki
K
Wu
Fei
F
Kim
Eui Ho
EH
Soma
Toshihiro
T
Tamaki
Hiroya
H
Kawakami
Manabu
M
Oji
Yusuke
Y
Hosen
Naoki
N
Kubota
Takeshi
T
Nakagawa
Masashi
M
Yamagami
Tamotsu
T
Hiraoka
Akira
A
Tsukaguchi
Machiko
M
Udaka
Keiko
K
Ogawa
Hiroyasu
H
Kishimoto
Tadamitsu
T
Nomura
Taisei
T
Sugiyama
Haruo
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood*; D000917:Antibody Formation / Q000502:physiology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D017578:Immunoglobulin Class Switching / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D025721:WT1 Proteins / Q000276:immunology* / Q000378:metabolism
D000912:Antibodies, Neoplasm; D025721:WT1 Proteins