SS1P is an immunotoxin comprised of the variable fragment of a mesothelin-targeted antibody linked to a bacterial toxin. Although SS1P induces apoptosis in mesothelioma cell lines, which express mesothelin, only minor antitumour activity was observed in Phase I trials in patients with mesothelioma, primarily because patients developed neutralizing antibodies to SS1P. To circumvent this, Hassan et al. treated patients with pentostatin and cyclophosphamide to deplete B cells and T cells prior to SS1P treatment. This regimen resulted in major tumour regression in three of ten patients with chemotherapy-refractory mesothelioma.
References
Hassan, R. et al. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci. Transl Med. 5, 208ra147 (2013)
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Seton-Rogers, S. Improved efficacy. Nat Rev Cancer 13, 823 (2013). https://doi.org/10.1038/nrc3643
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DOI: https://doi.org/10.1038/nrc3643