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Sredi sluchayev trizhdy negativnogo raka molochnoy zhelezy (TNRMZH) preobladayut novoobrazovaniya s povyshennoy ekspressiyey poverkhnostnogo antigena mezotelina (MSLN) — odnoy iz predpochtitel'nykh misheney dlya napravlennoy terapii mnogikh vidov solidnykh opukholey. Razrabotka MSLN-oposredovannoy terapii TNRMZH oslozhnena tem, chto bol'shaya chast' perevivayemykh kletochnykh kul'tur etogo subtipa MSLN-negativny. Tsel'yu raboty bylo nayti giperekspressiruyushchiye MSLN model'nyye kletochnyye kul'tury TNRMZH i poluchit' novyye odnodomennyye antitela (nanoantitela), raspoznayushchiye MSLN na kletkakh TNRMZH. Urovni transkripta mezotelina byli opredeleny na paneli kletochnykh liniy TNRMZH pri pomoshchi OT- PTSR-RV, rezul'taty verifitsirovany nepryamym immuno-fermentnym analizom na megakariotsit-potentsiruyushchiy faktor, sekretiruyemuyu chast' belka- predshestvennika mezotelina. Dlya polucheniya nanoantitel adaptirovali metod predvaritel'nogo obogashcheniya immunnykh bibliotek fragmentov VHH- antitel iz mononuklearov Vicugna pacos s selektsiyey pri pomoshchi fagovogo displeya. V rezul'tate issledovaniya polucheny dva varianta nanoantitel, obladayushchikh vysokoy spetsifichnost'yu vzaimodeystviya s mishen'yu i Kd okolo 140 i 95 nmol'. Byli identifitsirovany dve linii kletok MSLN+ i tri linii MSLN– TNRMZH. Nanoantitela okazalis' sposobny raspoznavat' tselevoy antigen na MSLN+ kletkakh i obladali nizkim urovnem svyazyvaniya s MSLN–-kletochnymi kul'turami. Ustanovlena udobnaya kletochnaya model' MSLN+ TNRMZH dlya testirovaniya MSLN-oposredovannoy terapii; novyye odnodomennyye antitela mogut byt' ispol'zovany v kachestve natselivayushchikh chastey khimernykh antigennykh retseptorov.

Novyye odnodomennyye antitela k mezotelinu i kletochnyye modeli dlya razrabotki targetnoy terapii raka molochnoy zhelezy