Biological response modifiers as adjuvants in monoclonal antibody-based treatment (review).
Compelling experimental evidence suggest that the use of differentiation-inducing agents which enhance tumor antigen expression may play a pivatal role in MAb-based approaches to tumor diagnosis and/or therapy. In particular, interferons can up-regulate CEA and TAG-72 expression on the surface of human carcinoma cells which leads to an enhanced MAb tumor localization. The ability to target additional MAb to the tumor site has subsequently been shown to augment radioimmunodetection and therapy in experimental models. Initial clinical studies reported that interferon administration to patients diagnosed with malignant melanoma improved the tumor distribution of antimelanoma MAb without an accompanying increase of antibody in normal tissues. The findings from our phase 1A trial clearly showed that intracavitary IFN-gamma administration augmented TAG-72 and CEA expression on carcinoma cells isolated from malignant ascites from patients diagnosed with ovarian or gastrointestinal cancer. Future efforts need to further investigate the molecular mechanisms involved in the regulation of these and other human tumor antigens by the interferons as well as other differentiation-inducing agents. Additional clinical studies should evaluate the overall effectiveness of combining an antigen up-regulation protocol with a conjugated MAb in the hope of improving tumor diagnosis and therapy.
Guadagni
F
F
Regina Elena Cancer Institute, Rome, Italy.
Roselli
M
M
Nieroda
C
C
Dansky-Ullmann
G
G
Schlom
J
J
Greiner
J W
JW
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000276:immunology; D003110:Colonic Neoplasms / Q000628:therapy*; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use; D015850:Interleukin-6 / Q000502:physiology; D010051:Ovarian Neoplasms / Q000628:therapy*; D016499:Radioimmunotherapy; D015398:Signal Transduction; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D002272:Carcinoembryonic Antigen; D007155:Immunologic Factors; D015850:Interleukin-6; D007371:Interferon-gamma; D000242:Cyclic AMP