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Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma.

AbstractPURPOSE:
CMC-544 is a CD22-targeted immunoconjugate of calicheamicin and exerts a potent cytotoxic effect against CD22+ B-cell lymphoma. This study evaluated antitumor efficacy of CMC-544 against systemically disseminated B-cell lymphoma.
EXPERIMENTAL DESIGN:
Scid mice received i.v. injections of CD22+ Ramos B-cell lymphoma cells for their systemic dissemination. CMC-544, G5/44, CD33-targeted CMA-676 (control conjugate) or rituximab were given i.p. 3, 9, 15, or 21 days after B-cell lymphoma dissemination. Diseased mice were monitored daily for hind-limb paralysis and death. Histopathological examination of CMC-544-treated and vehicle-treated diseased mice was also performed.
RESULTS:
Mice with disseminated B-cell lymphoma developed hind-limb paralysis within 35 days. When given up to 15 days after B-cell lymphoma dissemination, CMC-544 extended survival of the diseased mice to >100 days, and these mice were considered cured. CMC-544 was efficacious when given during both the early initiation phase and the late established phase of the disease. A single dose of CMC-544 was effective in delaying the occurrence of hind-limb paralysis. In contrast, neither CMA-676 nor unconjugated G5/44 was effective. Rituximab was effective when given early in the disease process but not when the disease was established. Histopathological analysis revealed B-cell lymphoma infiltration in brain, spinal cord, bone marrow, and kidney in vehicle-treated but not in CMC-544-treated diseased mice. Consistent with its efficacy against the disseminated B-cell lymphoma, CMC-544 also caused regression of established Ramos B-cell lymphoma xenografts in scid mice.
CONCLUSIONS:
CMC-544 confers strong therapeutic activity against systemic disseminated B-cell lymphoma and protects mice from hind-limb paralysis and death. These results support clinical evaluation of CMC-544 in the treatment of CD22+ lymphoid malignancies.
AuthorsJohn F DiJoseph, Mary E Goad, Maureen M Dougher, Erwin R Boghaert, Arthur Kunz, Philip R Hamann, Nitin K Damle
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 24 Pg. 8620-9 (Dec 15 2004) ISSN: 1078-0432 [Print] United States
PMID15623646 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD22 protein, human
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Immunoconjugates
  • Immunoglobulin G
  • Lectins
  • Sialic Acid Binding Ig-like Lectin 2
  • Rituximab
  • Inotuzumab Ozogamicin
Topics
  • Animals
  • Antibodies, Monoclonal (therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD (metabolism)
  • Antigens, Differentiation, B-Lymphocyte (metabolism)
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Cell Adhesion Molecules (metabolism)
  • Hindlimb
  • Humans
  • Immunoconjugates (therapeutic use)
  • Immunoglobulin G (metabolism)
  • Immunotherapy (methods)
  • Inotuzumab Ozogamicin
  • Lectins (metabolism)
  • Lymphoma, B-Cell (metabolism, pathology, therapy)
  • Male
  • Mice
  • Mice, SCID
  • Paralysis (etiology)
  • Rituximab
  • Sialic Acid Binding Ig-like Lectin 2
  • Survival Rate
  • Transplantation, Heterologous

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