Russian Journal of Bioorganic Chemistry. Vol. 51, No. 5, Pages 2089-2099, 2025

M. V. Larina^a^,*, Yu. P. Finashutina^b, N. A. Kravchuk^b, V. A. Misyurin^b, V. N. Novoseletsky^c, D. S. Balabashin^a, O. N. Solopova^b, D. V. Sokolova^b, V. S. Pokrovsky^b, D. A. Dolgikh^{a, d}, T. K. Aliev^{a, e}, A. V. Misyurin^f, and M. P. Kirpichnikov^{a, c}

^aShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia

^bN. N. Blokhin National Medical Research Center of Oncology, Moscow, 115478 Russia

^eFaculty of Chemistry, Lomonosov Moscow State University, Moscow, 119234 Russia

^fVavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117437 Russia

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.

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