A cytotoxic agent can be generated selectively at cancer sites View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1988-12

AUTHORS

K D Bagshawe, C J Springer, F Searle, P Antoniw, S K Sharma, R G Melton, R F Sherwood

ABSTRACT

Attempts to improve the selectivity of anti-cancer agents by conjugating them to antibodies directed at tumour associated antigens have demonstrated tumour localisation but only limited therapeutic success. We report here the advantage of a 2-stage approach in which the first component combines the selective delivery of antibody with a capability to generate a cytotoxic agent from a second subsequently administered component. A bacterial enzyme, carboxypeptidase G2 (CPG2) was conjugated with F(ab')2 fragment of a monoclonal antibody directed at beta subunit of human chorionic gonadotrophin (beta-hCG) and injected into nude mice bearing hCG producing CC3 xenografts of human choriocarcinoma. Time was allowed for the conjugate to localise at tumour sites and clear from blood before injecting para-N-bis (2-chloroethyl) aminobenzoylglutamic acid. Cleavage of the glutamic acid moiety from this molecule by CPG2 released a benzoic acid mustard. Growth of the tumour which is resistant to conventional chemotherapy was markedly depressed by a single course of treatment. This demonstrates for the first time the potential of an antibody directed enzyme to activate an alkylating agent and to eradicate an established human cancer xenograft. More... »

PAGES

bjc1988293

Journal

TITLE

British Journal of Cancer

ISSUE

6

VOLUME

58

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/bjc.1988.293

    DOI

    http://dx.doi.org/10.1038/bjc.1988.293

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1027398442

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/3265633


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