Cancer dormancy: lessons from a B cell lymphoma and adenocarcinoma of the prostate.
Cancer dormancy delineates a situation in which residual tumor cells persist in a patient with no apparent clinical symptoms. Although the precise mechanisms underlying cancer dormancy have not been explained, experimental models have provided some insights into the factors that might be involved in the induction and maintenance of a tumor dormant state. The authors of the present chapter studied a murine B cell lymphoma that can be made dormant when interacting with antibodies directed against the idiotype on its immunoglobulin Ig receptor. This experimental model of antibody-induced dormancy enabled the isolation and characterization of dormant lymphoma cells. The results indicated that anti-Ig antibodies activate growth-inhibiting signals that induced cycle arrest and apoptosis. This process appeared to be balanced by the growth of the tumor cells such that the tumor did not expand. In contrast, antibodies against HER-2expressed on prostate adenocarcinoma (PAC) cells were not growth inhibitory. However, an immunotoxin (IT) prepared by conjugating HER-2 to the A-chain of ricin (RTA) was internalized by PAC cells, followed by induction of cycle arrest and apoptotic death. Infusion of HER-2-specific IT into PAC-bearing immunodeficient mice did not eradicate the tumor but retained it dormant over an extended period of time. Hence, certain aspects of signaling receptors expressed on cancer can be manipulated by antibodies to induce and maintain a tumor dormant state.
Rabinovsky
Rosalia
R
Lautenberg Center for General and Tumor Immunology, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Uhr
Jonathan W
JW
Vitetta
Ellen S
ES
Yefenof
Eitan
E
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001943:Breast Neoplasms / Q000628:therapy; D002453:Cell Cycle / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007157:Immunologic Surveillance; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008954:Models, Biological; D018365:Neoplasm, Residual; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D012276:Ricin / Q000008:administration & dosage / Q000627:therapeutic use
D000888:Antibodies, Anti-Idiotypic; D000922:Immunotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011947:Receptors, Antigen, B-Cell; D012276:Ricin