Alton C. Morgan Jr., Robert W. Schroff (auth.), Kenneth A.'s Monoclonal Antibody Therapy of Human Cancer PDF

By Alton C. Morgan Jr., Robert W. Schroff (auth.), Kenneth A. Foon M.D., Alton C. Morgan Jr. PH.D. (eds.)

ISBN-10: 1461296420

ISBN-13: 9781461296423

ISBN-10: 1461326273

ISBN-13: 9781461326274

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Extra resources for Monoclonal Antibody Therapy of Human Cancer

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49 Table 9. Inhibition of cell survival following treatment with 791T/36-vindesine conjugate. Cell line Osteogenic sarcoma Antibody binding Percent inhibition of 75Se - me t uptake at following concentration: 40 ++ ++ + + 791T 788T 2 OS T 278 ~9/ml 20 75 59 ~9/ml 10 ~9:/ml 65 73 36 78 60 58 42 90 58 77 Melanoma RPMI 5966 Mel-57 2 5 2 10 3 2 Ovarian carcinoma PA-l 3 4 1 Bladder carcinoma T24 4 -14 0 5. THERAPEUTIC ACTIVITY OF 791T/36 MONOCLONAL ANTIBODY CONJUGATES The therapeutic potential of 791T/36 antibody conjugates is presently evaluated against human immunodeprived by thymectomy, tumor xenografts irradiation 9Gy), and cytosine arabinoside treatment.

Cell division so that the mean colony size showed minimal change I but the IC90 dose allowed colony growth to continue, albeit at a lower rate and incidence than in controls. These results show that the conjugate acted in a cytostatic rather than cytolytic fashion when the target cells were in a logarithmic growth phase. Cytostatic inhibition was most effective in single cells before division had occurred and was a relatively slow process in that many cells, exposed for 2 days to a partially toxic dose, could still recover in fresh growth medium.

43 The conjugate produced via the cis aconityl linkage (conjugate 3) did bind to 791T tumor cells as demonstrated by reaction of conjugate-treated cells with FITC-rabbit antimouse immunoglobulin (Table 6). Moreover, this uptake was specific since the conjugate did not bind to bladder carcinoma cells which do not express the 791T/36-defined epitope (18). In vitro cytotoxicity tests in which free daunomycin or antibody conjugates were incubated with tumor cells for 24 hours indicated that conjugate 1, in which daunomycin was directly linked to antibody, was the most reactive, showing about 10% of the level of cytotoxicity as free drug (Table 7).

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Monoclonal Antibody Therapy of Human Cancer by Alton C. Morgan Jr., Robert W. Schroff (auth.), Kenneth A. Foon M.D., Alton C. Morgan Jr. PH.D. (eds.)

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