Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation

UMMS Affiliation

Department of Quantitative Health Sciences

Publication Date


Document Type



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


Cancer Biology


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.


Cancer Res. 1995 Sep 15;55(18):4079-84.

Journal/Book/Conference Title

Cancer research


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