Monoclonal antibodies F36/22 and M7/l05 have been raised against human breast carcinoma cells. These antibodies localize human tumor xenografts which specifically express the corresponding target antigens. When passively administered, these McAbs produce a rapid and highly significant reduction in the volume of progressively growing human tumors implanted in athymic mice. The purpose of the proposed research is to extend these observations regarding the in vivo targeting and therapy of human tumor xenografts as generated both from primary tumor explants and characterized cell lines. The optimal therapeutic efficacies of passively-administered and drug-conjugated antibodies will be assessed regarding the following parameters, using tumor volume reduction as the endpoint: l) levels of antigen expression; 2) dosage and scheduling of antibodies; 3) initial tumor volume; 4) initial growth rate of the tumor; 5) the presence or absence of metastasis; and 6) the combined use of multiple McAbs. Studies on the ability of McAbs to deliver NMR-dense substances to tumor sites will also be performed. Using the tissue localization index as the endpoint, McAbs conjugated to iron-56 and fluorine-l9 metal chelates will be administered to animals bearing human tumor xenografts. McAbs will also be evaluated for their capacity to specifically remove carcinoma cells from bone marrow, as a pre-requisite for future autologous bone marrow rescue.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037646-03
Application #
3175435
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-08-15
Project End
1987-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
3
Fiscal Year
1986
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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