Autoantibody-mediated inhibition of pancreatic cancer cell growth in an athymic (nude) mouse model.
BACKGROUND
Antiribosomal P autoantibodies are detectable in 12-16% of patients with systemic lupus erythematosus.


OBJECTIVE
To assess whether antiribosomal P autoantibodies could be useful as a novel form of immunotherapy for pancreatic cancer.


METHODS
Three pancreatic cancer cell lines were incubated with antiribosomal P or normal human immunoglobulin. Viability was assayed with MTT, and apoptosis was detected by TUNEL. MIA PaCa-2 cells were injected into athymic mice. Animals were treated with intraperitoneal antibody or control immunoglobulin. Serum antibody levels were measured by ELISA. Tumor nodule size was measured weekly. Binding of the antibody to tumors was demonstrated with fluorescent microscopy.


RESULTS
Antiribosomal P antibody inhibited pancreatic cancer cell proliferation up to 54.6% (p < 0.01) and was associated with a threefold increase in the rate of apoptosis (p < 0.05). Tumor volume after 4 weeks of treatment was 23.2 mm3, versus 141.5 mm3 for the control group (p < 0.05). Apoptosis rate within the nodules was increased twofold, to 11.4%, in comparison with control (p < 0.05).


CONCLUSIONS
Antiribosomal P autoantibody at levels similar to those that can exist in SLE inhibits the growth of pancreatic cancer cells, in vitro and in vivo. The mechanism involves surface binding and apoptosis.
Gardner-Thorpe
James
J
Department of Gastrointestinal and General Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ito
Hiromichi
H
Ashley
Stanley W
SW
Whang
Edward E
EE
D000818:Animals; D000918:Antibody Specificity; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015800:Protozoan Proteins; D012269:Ribosomal Proteins / Q000276:immunology; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D001323:Autoantibodies; C064601:L12E protein, Trypanosoma cruzi; D015800:Protozoan Proteins; D012269:Ribosomal Proteins