Tu110 - anti-cd45rc Mab Treatment Improves Experimental Inflammatory Bowel Disease (IBD)

Séverine Ménoret – Nantes Université, INSERM UMR1064-CR2TI; Bérangère Evrard – Nantes Université, INSERM UMR1064-CR2TI; Marine Besnard – Nantes Université, INSERM UMR1064-CR2TI; Apolline Salama – Nantes Université, INSERM UMR1064-CR2TI; Nadège Vimont – AbolerIS Pharma; Laure-Hélène Ouisse – Nantes Université, INSERM UMR1064-CR2TI; Elise Brisebard – APEX-UMR703 PAnTher INRA/ONIRIS; Thibault Larcher – APEX-UMR703 PAnTher INRA/ONIRIS; Laetitia Baucoult – Nantes Université, INSERM, CNRS, UMR1064-CR2TI; Jean-François Mosnier – CHU Nantes; Arnaud Bourreille – CHU Nantes; Carole Guillonneau – Nantes Université, INSERM, CNRS, UMR1064-CR2TI

Abstract Text: IBD needs new treatments that could better control disease. Anti-CD45RC mAb-mediated depletion of Tconv and B CD45RChigh cells as well as increased CD45RCneg/low Treg numbers and function. These effects prevent tissue destruction while preserving protective immune responses in animal models of organ transplantation, GVHD and APECED, as well as with human cells in in vivo mouse immune humanized models and in vitro.
In a model of colitis by transfer of CD4+CD45RChigh T cells into immunodeficient rats, anti-CD45RC mAb treatment resulted in significant survival at day 50 vs. isotype control-treated rats (8/9 animals vs. 0/7, respectively, with death before day 32). Treatment was associated to significant decreases in T cells vs. controls for both blood and spleen (8.3 and 2.7-fold, respectively) as well as for colon lesions’ scores (1±0.4 vs. 3.2±0.5, respectively).
In blood from Crohn’s disease (CD) and ulcerative colitis (UC) patients CD45RChigh and CD45RClow/neg cells were observed in the T and B cell compartments in proportions roughly comparable to the ones in healthy controls (HC). Anti-CD45RC mAb induced apoptosis in vitro of T and B CD45RChigh (but not of CD45RClow/neg) cells from CD and UC patients comparable to the ones for HC. Immunohistology analyses of gut biopsies from CD and UC patients showed the presence of CD45RC+ cells among both T and B cells (~25 and ~80 % of them, respectively).
In conclusion, animal models and clinical data support the potential of anti-CD45RC mAb for treatment of IBD patients.