An imaging-based rapid evaluation method for complement-dependent cytotoxicity discriminated clinical response to rituximab-containing chemotherapy.
OBJECTIVE
Rituximab has greatly improved the efficacy of chemotherapy regimens for CD20-positive non-Hodgkin's lymphoma. However, although several mechanisms of action of rituximab have been identified, the exact therapeutic functions of these mechanisms remains to be clarified. In addition, there is no established prognostic marker to predict an individual response. This study verified the validity of ex vivo complement-dependent cytotoxicity (CDC) susceptibility as a predictor of pathologic tumor regression in patients undergoing rituximab-containing chemotherapy and examined whether CDC contributes to the mechanism of action of rituximab.


METHODS
A rapid assay system was established to evaluate the tumoricidal activity of rituximab using a living cell-imaging technique. We analyzed lymph node biopsies obtained from 234 patients with suspected lymphomas and estimated the association between CDC susceptibility and the response to rituximab-containing chemotherapy in diffuse large B-cell lymphoma and follicular lymphoma.


RESULTS
This study revealed that CDC susceptibility of lymphoma cells freshly obtained from patients was strongly associated with response to rituximab-containing chemotherapy in both diffuse large B-cell lymphoma and follicular lymphoma. This correlation was not apparent in cases that received chemotherapy without rituximab.


CONCLUSIONS
The system that we have established allows a successful assessment of rituximab-induced CDC and can distinguish cases refractory to rituximab-containing chemotherapy. The association between CDC susceptibility and therapy response suggests that CDC is pivotal in the ability of chemotherapy including rituximab to induce remission.
Mishima
Yuji
Y
Olympus Bio-Imaging Laboratory, Clinical Chemotherapy, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Sugimura
Natsuhiko
N
Matsumoto-Mishima
Yuko
Y
Terui
Yasuhito
Y
Takeuchi
Kengo
K
Asai
Suzuka
S
Ennishi
Daisuke
D
Asai
Hiroaki
H
Yokoyama
Masahiro
M
Kojima
Kiyotsugu
K
Hatake
Kiyohiko
K
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods*; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D012372:ROC Curve; D015203:Reproducibility of Results; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D003165:Complement System Proteins