PMID: 8611717May 1, 1996Paper

Cure of multidrug-resistant human B-cell lymphoma xenografts by combinations of anti-B4-blocked ricin and chemotherapeutic drugs.

Blood
C LiuR O'Connor

Abstract

The CD-19-directed immunotoxin anti-B4-blocked ricin (anti-B4-bR) is currently in clinical trials for the treatment of B-cell malignancies. To explore the potential of using anti-B4-bR with chemotherapy protocols we tested the in vivo efficacy of the immunotoxin in combination with two multi-drug chemotherapeutic regimens in severe combined immunodeficient (SCID) mice bearing disseminated tumors of the multidrug-resistant human B-cell lymphoma Namalwa/mdr-1. In cytotoxicity studies in vitro, combinations of the immunotoxin with cisplatin produced supra-additive killing effects on both Namalwa and Namalwa/mdr-1 cells, whereas anti-B4-bR combined with 4-hydroperoxy-cyclophosphamide caused additive killing of both cell lines. In vivo cyclophosphamide, cisplatin, vincristine, doxorubicin, and etoposide as single agents, were effective in prolonging the survival of SCID mice burdened with the Namalwa tumor, whereas only cyclophosphamide and cisplatin were effective on Namalwa/mdr-1 tumors. Treatment of Namalwa/mdr-1-bearing mice with anti-B4-bR alone or with the drug combination CHOE (consisting of cyclophosphamide, vincristine, doxorubicin, and etoposide) alone increased the lifespan of the tumor-burdened mice by 58% and 73%, respe...Continue Reading

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