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Cancer Immunology, Immunotherapy

, Volume 34, Issue 2, pp 90–96 | Cite as

Regression of human melanoma xenografts in nude mice injected with methotrexate linked to monoclonal antibody 225.28 to human high molecular weight-melanoma associated antigen

  • Tarun Ghose
  • Soldano Ferrone
  • A. Huntley Blair
  • Yaroslav Kralovec
  • Massimo Temponi
  • Mandip Singh
  • Moll Mammen
Original articles

Summary

Intravenous injections into nude mice of 5 mg/kg methotrexate (MTX) linked to the antibody to human high molecular weight-melanoma associated antigen (HMW-MAA), monoclonal antibody (mAb) 225.28, an IgG2a, on days 1, 4, 7, 10 and 14, starting 24 h after subcutaneous inoculation of 2 × 106 cultured human M21 melanoma cells inhibited mean tumor volume by 90% on day 14 and by 65% on day 50 after the beginning of the treatment. Injections of equimolar amounts of free MTX and MTX linked to normal mouse IgG or to an isotypematched myeloma protein did not inhibit tumor growth significantly. MTX linked to mAb 225.28 did not inhibit the xenograft of a subline of human melanoma cell line M21 without detectable expression of HMW-MAA. In a clonogenic assay, the MTX-225.28 conjugate was three times more potent in inhibiting the growth of M21 melanoma cells than free MTX, but did not inhibit the growth of kidney carcinoma cells Caki-1, which do not express high-Mr MAA. In contrast, MTX linked to the mAb DAL K29, reacting with kidney carcinoma cells Caki-1, inhibited their growth but did not affect that of melanoma cells. M21 melanoma cells isolated from the residual tumor of a mouse treated with the MTX-225.28 conjugate did not differ in their reactivity with mAb 225.28 and in their sensitivity to MTX when compared with M21 cells from an untreated mouse.

Key words

Methotrexate Monoclonal antibody Immunoconjugate Melanoma 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Tarun Ghose
    • 1
  • Soldano Ferrone
    • 2
  • A. Huntley Blair
    • 3
  • Yaroslav Kralovec
    • 3
  • Massimo Temponi
    • 2
  • Mandip Singh
    • 4
  • Moll Mammen
    • 1
  1. 1.Departments of PathologyDalhousie UniversityHalifaxCanada
  2. 2.Department of Microbiology and ImmunologyNew York Medical CollegeValhallaUSA
  3. 3.Departments of BiochemistryDalhousie UniversityHalifaxCanada
  4. 4.Departments of College of PharmacyDalhousie UniversityHalifaxCanada

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