Both the incidence and mortality of malignant melanoma are rising at a rate now estimated to double every 10-15 years. Treatment of the advanced stages of the disease remains unsatisfactory, and new strategies are being sought. The development of monoclonal antibody technology and, more importantly, the recent demonstration of clinical response to the administration of monoclonal antibody in patients with advanced melanoma have stimulated renewed interest in the immunotherapy of this disease. This proposal is addressed at the further definition of the role of monoclonal antibodies in the diagnosis and treatment of malignant melanoma. All phases of the development of the antibodies are included, from the production and specificity testing, to in vitro evaluation of the specific biologic properties of the antibodies, including binding characteristics, direct cytostatic/cytotoxic effects, antibody mediated complement dependent cytotoxicity, and antibody dependent cellular cytotoxicity (ADCC). Further in vivo studies on localization and therapy in animal models will be performed after purification and safety testing. Promising antibodies will be introduced into clinical trials of localization and therapy. Therapeutic proposals include the administration of single antibodies, combinations of antibodies, concurrent antibody and various chemotherapeutic agents, and investigation of alternate routes of administration (eg intralymphatic, intra arterial isolation perfusion). Modifications of antibodies that do not mediate significant biologic effector functions are being investigated in other areas of the laboratory, and will be evaluated as the technology becomes available (eg antibody conjugates, class switching).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08CA001150-01
Application #
3079651
Study Section
(SRC)
Project Start
1986-04-15
Project End
1989-03-31
Budget Start
1986-04-15
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Memorial Hospital for Cancer & Allied Di
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021
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Coit, D G; Peters, M; Brennan, M F (1991) A prospective randomized trial of perioperative cefazolin treatment in axillary and groin dissection. Arch Surg 126:1366-71;discussion 1371-2
Jaques, D P; Coit, D G; Hajdu, S I et al. (1990) Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg 212:51-9