Eradication of Murine Lymphoma and Melanoma Cells by Chlorambucil‐Antibody Complexes

Weger, Roel A. de; Dullens, H. F. J.; Otter, W. Den

doi:10.1111/j.1600-065x.1982.tb00388.x

Cited by 14 publications

(3 citation statements)

References 32 publications

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“…Tumour cells were treated with immunotoxin in virro and then injected into mice to assess the survival of the animals. More recently malignant cells have been injected into the peritoneal cavity of mice and, after allowing time for tumour cells to graft, a variety of treatments were administered intraperitoneally (29,42,61). T h e results of such experiments have suggested that immunotoxins are more effective than either the appropriate controls or conventional chemotherapy, but neither type of experiment is a good model of the clinical problem which is faced in practice.…”

Section: W Pourorzmentioning

confidence: 99%

Drug Targeting-Current Aspects and Future Prospects

Pouton

2008

Journal of Clinical Pharmacy and Therapeutics

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A variety of materials have been suggested as carriers for the delivery of drugs to specific sites of action. Drugs may be covalently bound to carriers or physically trapped within particulate carriers. Likely mechanisms of action of targeting agents are described. The results of in vitro and in vivo experiments are reviewed and the prospective clinical uses of each type of carrier are discussed. In particular, monoclonal antibodies are promising agents for the targeting of cytotoxic agents to malignant cells. Radiolabelled monoclonal antibodies are likely to develop as agents for the radio‐imaging of tumours which will prove useful in the diagnosis and treatment of cancer.

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Section: W Pourorzmentioning

confidence: 99%

Drug Targeting-Current Aspects and Future Prospects

Pouton

2008

Journal of Clinical Pharmacy and Therapeutics

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“…These immunoconjugates have shown efficacy against tumor cells in vitro and, less frequently, against tumor in vivo in animals [27, 30, 38, 43, 50, 54-57, 59, 61]. In addition, small drugs currently used for the treatment of neoplasia have been conjugated to MCA or polyclonal antisera and have shown some efficacy against animal tumors in vivo [1,13,40,41,46,47,51]. A large number of these animal tumor models have been human xenografts in congenitally athymic nude mice.…”

Section: Introductionmentioning

confidence: 99%

“…The advantages of using a syngeneic murine tumor model to test candidate immunotoxins are the rapidity and reproducibility of tumor development and the relative difficulty in achieving a cure because of the low numbers of cells required for a successful tumor growth [56,59]. Murine leukemias and lymphomas have been used by various groups as model systems for the study of immunotoxin efficacy, and success has been reported in some cases [13,43,51,55,56,59]. In this paper we report the development of an immunotoxin consisting of a conjugate of MCA to the Thy-1 antigen and the ribosome-inactivating protein gelonin, and its efficacy in vitro and in vivo in a syngeneic host against the murine thymic leukemia RADA.…”

Section: Introductionmentioning

confidence: 99%

The antileukemic efficacy of an immunotoxin composed of a monoclonal anti-Thy-1 antibody disulfide linked to the ribosome-inactivating protein gelonin

Scott

Goldmacher

Lambert

et al. 1987

Cancer Immunol Immunother

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We prepared an immunoconjugate consisting of a monoclonal antibody recognizing the Thy-1 antigen and the ribosome-inactivating protein gelonin linked by a disulfide bond. This immunotoxin preparation was judged to contain less than 5% free antibody or gelonin. It was highly toxic in vitro in an antigen-specific fashion to the Thy-1 expressing RADA leukemia of A/J mice. The IC50 of this preparation on RADA in vitro was 10(-12) M, while the IC50 on the Thy-1 negative S1509a fibrosarcoma of A/J mice was 10(-7) M. The toxicity of this immunoconjugate was also measured in a direct proliferation and it was found that a 4-h exposure and a 24-h exposure of RADA cells to a 1 nM concentration of immunotoxin killed 90% and 99.9% of cells, respectively. Furthermore, efficacy in vitro was not due to the intrinsic susceptibility of RADA cells to tis type of immunotoxin, as one prepared with gelonin and an antibody recognizing the TLa determinant on this leukemia had no efficacy in vitro. Clearance of the anti-Thy-1-gelonin immunoconjugate from the circulation of A/J mice after i.v. injection was rapid, especially during the first 8 h after injection, possibly because of binding to Thy-1 expressing tissue. Delivery of immunoconjugate to ascitic tumor in vivo was substantially better if the immunoconjugate was given by i.p. injection, rather than by the i.v. route. When given either i.v. or i.p. at the time of i.p. tumor inoculation in vivo, the anti-Thy-1-gelonin immunotoxin showed potency in an antigen-specific fashion; while this immunoconjugate prolonged survival and frequently cured RADA-inoculated mice, neither anti-Thy-1 antibody, gelonin, a combination of the two, nor immunotoxin of irrelevant specificity had any significant effect on survival. Anti-Thy-1-gelonin also had no effect on survival of A/J mice inoculated i.p. with S1509a. Furthermore, it was determined that a single i.p. dose of anti-Thy-1-gelonin killed 90% to 99% cells in vivo, and that the immunoconjugate was about as effective in this model as either adriamycin or cytoxan.

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