Abstract <p><b>Objective:</b> The PRAME antigen (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen expressed in various tumor types, represents an attractive target for targeted cancer therapy. <b>Methods:</b> A humanized antibody (6H8Hu) was developed based on the monoclonal antibody 6H8 specific to the PRAME protein. The antibody was produced in CHO cells. Results and Discussion: The humanized antibody retains the high affinity of the parental mAb to the antigen (1.2 nM), binds to both recombinant and native PRAME protein, inhibits the proliferation of the PRAME-positive human melanoma cell line Mel Ibr, and suppresses tumor nodule growth <i>in vivo</i> to a degree comparable to that of the murine antibody 6H8 and the cytostatic agent melphalan. <b>Conclusions:</b> The humanized antibody 6H8Hu is a promising candidate for targeted therapy against PRAME-positive melanoma, showing potential comparable to murine antibodies and conventional cytotoxic treatments.</p>

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Study of the Antiproliferative Activity of a Humanized Antibody to the Cancer-Testis Antigen PRAME

  • M. V. Larina,
  • Yu. P. Finashutina,
  • N. A. Kravchuk,
  • V. A. Misyurin,
  • V. N. Novoseletsky,
  • D. S. Balabashin,
  • O. N. Solopova,
  • D. V. Sokolova,
  • V. S. Pokrovsky,
  • D. A. Dolgikh,
  • T. K. Aliev,
  • A. V. Misyurin,
  • M. P. Kirpichnikov

摘要

Abstract

Objective: The PRAME antigen (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen expressed in various tumor types, represents an attractive target for targeted cancer therapy. Methods: A humanized antibody (6H8Hu) was developed based on the monoclonal antibody 6H8 specific to the PRAME protein. The antibody was produced in CHO cells. Results and Discussion: The humanized antibody retains the high affinity of the parental mAb to the antigen (1.2 nM), binds to both recombinant and native PRAME protein, inhibits the proliferation of the PRAME-positive human melanoma cell line Mel Ibr, and suppresses tumor nodule growth in vivo to a degree comparable to that of the murine antibody 6H8 and the cytostatic agent melphalan. Conclusions: The humanized antibody 6H8Hu is a promising candidate for targeted therapy against PRAME-positive melanoma, showing potential comparable to murine antibodies and conventional cytotoxic treatments.