Neoadjuvant therapy of gastric cancer with the human monoclonal IgM antibody SC-1: impact on the immune system.
Adjuvant therapies for minimal residual disease are a promising approach to improve the poor survival rates after surgery of gastric tumors. A pilot study of a neoadjuvant therapy was performed using a human monoclonal IgM antibody (SC-1) specifically inducing apoptosis in signet ring cell stomach carcinomas. However, scarce information exists on how such a treatment affects the immune system, in particular what are the effects of apoptosis induction and infusion of large amounts of IgM. Thus, the leukocyte composition (CD3, CD4, CD8, CD19, CD16+56, CD14) and several cytokines (TNF-alpha, IL6, IL12, IFN-gamma, GM-CSF, Neopterin) before and after SC-1 application were measured and compared to results of patients that underwent surgical removal of gastric carcinoma without antibody treatment. After SC-1 application, an increase in TNF-alpha and a decrease of lymphocytes and CD3+ T-cells but in the range obtained in healthy individuals was observed before surgery. After surgery, the IL6 levels increased and the TNF-alpha levels remained at the elevated level. Furthermore, there was a significant drop in lymphocytes and CD3+ T-cells. These effects were due to the surgical treatment. Other parameters did not show significant changes. It seems that the application of an apoptosis-inducing antibody prior to surgery of gastric tumors has mild if any effect on the immune system. Therefore, from an immunological point of view, the treatment with this monoclonal antibody is extremely safe.
Beutner
Ulrich
U
Department of Surgery I, Centre for Operative Medicine, University of Würzburg, D-97080 Würzburg, Germany.
Lorenz
Udo
U
Illert
Bertram
B
Rott
Loretta
L
Timmermann
Wolfgang
W
Vollmers
H Peter
HP
Müller-Hermelink
Hans Konrad
HK
Thiede
Arnulf
A
Ulrichs
Karin
K
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000032:analysis; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000009:adverse effects / Q000627:therapeutic use; D007958:Leukocyte Count; D007962:Leukocytes / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010865:Pilot Projects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D016207:Cytokines; D007075:Immunoglobulin M; C111124:SC-1 monoclonal antibody