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Article
Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation
Women’s Health Research Faculty Publications
  • Ravi V. J. Chari, ImmunoGen, Inc.
  • Kristin A. Jackel, ImmunoGen, Inc.
  • Lizabeth A. Bourret, ImmunoGen, Inc.
  • Susan M. Derr, ImmunoGen, Inc.
  • B. Mitra Tadayoni, ImmunoGen, Inc.
  • Kristin M Mattocks, University of Massachusetts Medical School Worcester
  • Sudhir A. Shah, ImmunoGen, Inc.
  • Changnian Liu, ImmunoGen, Inc.
  • Walter A. Blattler, ImmunoGen, Inc.
  • Victor S. Goldmacher, ImmunoGen, Inc.
UMMS Affiliation
Department of Quantitative Health Sciences
Date
9-15-1995
Document Type
Article
Subjects
Animals; Antibiotics, Antineoplastic; Antigens, CD; Antigens, CD19; Antigens, CD56; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, T-Lymphocyte; Female; Humans; Immunotoxins; *Indoles; Leucomycins; Lymphoma, B-Cell; Mice; Mice, SCID; Tumor Cells, Cultured
Disciplines
Abstract
Bis-indolyl-(seco)-1,2,9a-tetrahydrocyclopropa[c]benz[e]indol-4-on e compounds are synthetic analogues of CC-1065 that are highly cytotoxic toward a broad spectrum of tumor cell lines. One of these compounds, called DC1, was conjugated to antibodies via novel cleavable disulfide linkers. Conjugates of DC1 with murine mAbs anti-B4 and N901 directed against tumor-associated antigens CD19 and CD56, respectively, proved to be extremely potent and antigen selective in killing target cells in culture. DC1 conjugates with humanized versions of anti-B4 and N901 antibodies were also constructed and demonstrated to be as cytotoxic and selective as the respective murine antibody conjugates. The anti-B4-DC1 conjugate showed antitumor efficacy in an aggressive metastatic human B-cell lymphoma survival model in SCID mice and completely cured animals hearing large tumors. Anti-B4-DC1 was considerably more effective in this tumor model than doxorubicin, cyclophosphamide, etoposide, or vincristine at their maximum tolerated doses.
Rights and Permissions
Citation: Cancer Res. 1995 Sep 15;55(18):4079-84.
Comments

At the time of publication, Kristin Mattocks was not yet affiliated with the University of Massachusetts Medical School.

Related Resources
Link to Article in PubMed
PubMed ID
7545085
Citation Information
Ravi V. J. Chari, Kristin A. Jackel, Lizabeth A. Bourret, Susan M. Derr, et al.. "Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation" Vol. 55 Iss. 18 (1995) ISSN: 0008-5472 (Linking)
Available at: http://works.bepress.com/kristin_mattocks/14/