CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells.
We studied the effect of CMC-544, the calicheamicin-conjugated anti-CD22 monoclonal antibody, used alone and in combination with rituximab, analyzing the quantitative alteration of target molecules, that is, CD20, CD22, CD55 and CD59, in Daudi and Raji cells as well as in cells obtained from patients with B-cell malignancies (BCM). Antibody inducing direct antiproliferative and apoptotic effect, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) were tested separately. In Daudi and Raji cells, the CDC effect of rituximab significantly increased within 12 h following incubation with CMC-544. The levels of CD22 and CD55 were significantly reduced (P<0.001 in both cells) after incubation with CMC-544, but CD20 level remained constant or increased for 12 h. Similar results were obtained in cells from 12 patients with BCM. The antiproliferative and apoptotic effect of CMC-544 were greater than that of rituximab. The ADCC of rituximab was not enhanced by CMC-544. Thus, the combination of CMC-544 and rituximab increased the in vitro cytotoxic effect in BCM cells, and sequential administration for 12 h proceeded by CMC-544 was more effective. The reduction of CD55 and the preservation of CD20 after incubation with CMC-544 support the rationale for the combined use of CMC-544 and rituximab.
Takeshita
A
A
Department of Laboratory Medicine, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan. akihirot@hama-med.ac.jp
Yamakage
N
N
Shinjo
K
K
Ono
T
T
Hirano
I
I
Nakamura
S
S
Shigeno
K
K
Tobita
T
T
Maekawa
M
M
Kiyoi
H
H
Naoe
T
T
Ohnishi
K
K
Sugimoto
Y
Y
Ohno
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D000080045:Inotuzumab Ozogamicin; D016393:Lymphoma, B-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D017931:DNA Primers; D051918:Sialic Acid Binding Ig-like Lectin 2; D000080045:Inotuzumab Ozogamicin