Cancer Chemother Pharmacol (2011) 67:741–749 DOI 10.1007/s00280-010-1342-9 123 ORIGINAL ARTICLE Preclinical anti-tumor activity of antibody-targeted chemotherapy with CMC-544 (inotuzumab ozogamicin), a CD22-speciWc immunoconjugate of calicheamicin, compared with non-targeted combination chemotherapy with CVP or CHOP John F. DiJoseph · Maureen M. Dougher · Deborah Y. Evans · Bin-Bing Zhou · Nitin K. Damle Received: 14 December 2009 / Accepted: 22 April 2010 / Published online: 3 June 2010  Springer-Verlag 2010 Abstract Purpose CMC-544 (inotuzumab ozogamicin) is a CD22- speciWc immunoconjugate of calicheamicin currently being evaluated in patients with non-Hodgkin’s B-cell lymphoma (BCL). CHOP and CVP represent untargeted combination chemotherapy comprised of cyclophosphamide, vincristine and prednisone with or without doxorubicin, commonly used in the treatment of NHL. Here, we describe anti-tumor eYcacy of CMC-544, CHOP or CVP against human BCL xenografts. Methods In vitro, human BCLs were cultured with CMC- 544 or individual constituents of CHOP for inhibition of their growth. In vivo, immunocompromised mice with established BCL xenografts were administered CHOP, CVP or CMC-544 to monitor their survival and BCL growth. Results In vitro, CMC-544 was more potent in causing growth inhibition of various BCL than cyclophosphamide, doxorubicin, vincristine or dexamethasone. In vivo, treatment with CHOP or CVP inhibited growth of BCL xenografts for up to 40 days after which BCL relapsed. Tumor growth inhibition by CMC-544 (>100 days) lasted longer than that by CHOP or CVP. BCL xenografts that relapsed after the treatment with CHOP or CVP were far less responsive to CHOP or CVP re-treatment but regressed upon subsequent treatment with CMC-544. CVP could be co-administered with suboptimal doses of CMC-544, while CHOP could be administered on alternant days with CMC-544 to cause enhanced regression of established BCL xenografts. Conclusion Preclinically, CMC-544 provides greater therapeutic beneWt than CVP or CHOP against BCL xeno- grafts. CMC-544 may also be co-administered with stan- dard chemotherapeutic regimens in the treatment of B-NHL for superior anti-tumor activity. Keywords CD22 · CMC-544 · CHOP · CVP · Immunoconjugate · B-cell lymphoma Abbreviations BCL B-cell lymphoma CalichDMH N-acetyl gamma calicheamicin dimethyl hydrazide CHOP Cyclophosphamide doxorubicin vincristine prednisone CVP Cyclophosphamide vincristine prednisone B-NHL Non-Hodgkin’s B-cell lymphoma Introduction Combination chemotherapy using cytotoxic agents with distinct mechanisms of action is a common therapeutic strategy in the treatment of metastatic cancers. Individual components of the cytotoxic combination chemotherapy All authors were employees of Wyeth Research during the conduct of this investigation. CMC-544 is a collaboration product being jointly developed by Wyeth Research and UCB Celltech, Slough, UK. J. F. DiJoseph (&) · M. M. Dougher · D. Y. Evans · B.-B. Zhou · N. K. Damle Oncology Discovery, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA e-mail: dijosej@wyeth.com Present Address: N. K. Damle Endo Pharmaceuticals, 100 Endo Boulevard, Chadds Ford, PA 19317, USA