Monoclonal antibody F36/22 (IgG3, recognizes a glycoprotein with Mr of 700-1000K) has been shown immunohistochemically to be reactive with all human common epithelial ovarian cancers, while normal ovary expresses no detectable level of immunostain. Human exfoliated ovarian tumor cells are usually disseminating throughout the entire peritoneal cavity, and represent an ideal target for therapeutic manipulation in a confined compartment. A recently available human ovarian carcinoma xenograft in female athymic mice, NIH:OVCAR_3, expresses antigen recognized by monoclonal antibody F36/22 and resembles the human disease by producing ascites and intra-abdominal carcinomatosis. Using monoclonal antibody F36/22 as the probe and NIH:OVCAR-3 as the in vivo model, we will develop and eva;iate effective radioimmunotherapy for the targeting and elimination of peritoneal ovarian tumor seedings. Adriamycin, acommonly used cytotoxic agent in ovarian cancer, will be conjugated to monoclonal antibody F36/22 as the probe and NIH:OVCAR as the in vivo model, we will develop and evaluate effective radioimmunotherapy for the targeting and elimination of peritoneal ovarian tumor seedings. Adriamycin, a commonly used cytotoxic agent in ovarian cancer, will be conjugated to monoclonal antibody F36/22 for intracavity immunochemotherapy of ovarian tumor. Effectiveness of both therapies will be potentiated by biological response modifiers. The proposed approaches to the use of a unique monoclonal antibody in targeting and therapy of ovarian cancer in a confined cavity compartment with little or no communication with toher body compartments will generate defined and useful preclinical information.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037646-05
Application #
3175436
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-08-15
Project End
1991-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Nakajima, I; Chu, T M (1992) Enhanced cell-mediated cytotoxicity by interferon-gamma and interleukin-2 against syngeneic murine mammary adenocarcinoma. Mol Biother 4:47-52
Lin, T H; Chu, T M (1992) Enhancement of protein kinase C in murine lymphokine-activated killer cells by retinoic acid. J Biol Chem 267:1335-9
Nakajima, I; Chu, T M (1991) Synergistic antitumor activity of interleukin-2 and cimetidine against syngeneic murine tumor. Cancer Immunol Immunother 33:9-14
Ohnishi, H; Lin, T H; Nakajima, I et al. (1991) Prostaglandin E2 from macrophages of murine splenocyte cultures inhibits the generation of lymphokine-activated killer cell activity. Tumour Biol 12:99-110
Ohnishi, H; Lin, K M; Chu, T M (1990) Prolongation of serum half-life of interleukin 2 and augmentation of lymphokine-activated killer cell activity by pepstatin in mice. Cancer Res 50:1107-12
Nakajima, I; Chu, T M (1990) Prostaglandin E2-mediated suppression of murine lymphokine-activated killer cell activity generated from tumor-bearing hosts by interferon-gamma. Mol Biother 2:228-32
Chao, T Y; Ohnishi, H; Chu, T M (1990) Indirect inhibition of generation of murine lymphokine-activated killer cell activity in splenocyte cultures by interferon-gamma. Immunology 70:116-20
Lin, T H; Chu, T M (1990) Enhancement of murine lymphokine-activated killer cell activity by retinoic acid. Cancer Res 50:3013-8
Chu, T M; Kawinski, E; Hibi, N et al. (1989) Prostate-specific antigenic domain of human prostate specific antigen identified with monoclonal antibodies. J Urol 141:152-6
Chu, T M; Constantine, R; Nemoto, T (1989) Serum level of cryptic tumor antigens in breast cancer patients as determined by two monoclonal antibodies (M85/F36) and its comparison with CA 15-3. J Clin Lab Anal 3:267-72

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