The effect of an anti-membrane antibody-methotrexate conjugate on the human prostatic tumour line PC3

Aj, Rowland; Me, Harper; Dw, Wilson; Griffiths, K.

doi:10.1038/bjc.1990.158

Cited by 3 publications

(1 citation statement)

References 27 publications

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“…Relatively low potency of MTX as a payload can be ameliorated by increasing the drug to antibody ratio (DAR), while maintaining acceptable biological activity of the mAb. Reported DAR values for MTX-based ADCs depend on available lysyl and arginyl side chains in antibody molecules and range from 10 to 14.6 [23,32]. In the present work, an even higher DAR value was obtained by MTX anhydride crosslinking reaction.…”

Section: Discussionmentioning

confidence: 52%

An Antibody Specific for the Dog Leukocyte Antigen DR (DLA-DR) and Its Novel Methotrexate Conjugate Inhibit the Growth of Canine B Cell Lymphoma

Lisowska

Milczarek

Ciekot

et al. 2019

Cancers

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Canine B-cell lymphoma (CBL) is an incurable, spontaneous lymphoid malignancy constituting an accurate animal model for testing novel therapeutic strategies in human medicine. Resources of available species-specific therapeutic monoclonal antibodies (mAbs) targeting CBL are scarce. The aim of the present study was to evaluate the therapeutic potential of mAb B5, specific for the dog leukocyte antigen DR (DLA-DR) and its antibody-drug conjugate with methotrexate (B5-MTX). B5 induced caspase-dependent apoptosis of DLA-DR-expressing canine B cell lymphoma/CLBL1 and CLB70 leukemia lines, but not the GL-1 line not expressing DLA-DR. The cytotoxicity of B5-MTX to sensitive cells was further potentiated by a payload of MTX, but without any substantial off-target effects. The infusion of B5 and B5-MTX in a murine model of disseminated, advanced canine lymphoma, mediated >80% and >90% improvement in survival, respectively, and was well tolerated by the animals. Interestingly, the concentrations of soluble DLA-DR (sDLA-DR) antigens present in the blood serum of tumor-bearing mice were found proportional to the tumor burden. On this basis, sDLA-DR levels were evaluated as a potential biomarker using samples from canine lymphoma patients. In summary, the action of B5 and B5-MTX holds promise for further development as an alternative/complementary option for the diagnosis and treatment of canine lymphoma.

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Section: Discussionmentioning

confidence: 52%