Functional human myeloid compartment in BRGSF-HIS preclinical model
Additionally, anti-CD20 monoclonal antibody Rituximab (RTX) was administered to Flt3-L-boosted BRGSF-HIS mice to investigate its impact on circulating cells and splenocytes. RTX treatment induced a virtually complete depletion of circulating B cells at 48 hours, accompanied by a severe decrease in resident cells in the spleen (IgM+/IgD+ cells in CD19+ splenocytes). As RTX has been shown to bind via FcɣR (mostly FcɣRIIa and FcɣRIIIa), and triggers complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and ADCP1, these data suggest an efficient FcɣR mediated monocyte and NK cell cytotoxicity in BRGSF-HIS mice.
- Targeting human plasmacytoid dendritic cells (pDCs) in BRGSF-HIS
Another type of myeloid cells has been linked to autoimmune and inflammatory diseases, as well as some cancers: pDCs. In 2018, Fournier et al.2 described a new antibody, targeting pDC marker CD303, able to induce strong activity against these cells. This antibody’s in vivo efficacy was demonstrated in BRGSF-HIS mice. Indeed, a single administration of anti-CD303 antibody efficiently depleted circulating pDCs (90%). This depletion was less drastic in the spleen, and absent in the bone marrow. Interestingly, the authors also showed that anti-CD303 antibody depletes pDCs in vitro through ADCC and ADCP, and efficiently inhibits pDCs’ ability to secrete IFNα upon TLR9 stimulation. Taken together, these data suggest that, in vivo, pDC depletion is mediated by ADCC and ADCP, indicating once more that the BRGSF-HIS myeloid compartment is functional.
All these data converge to prove the functionality of BRGSF-HIS myeloid compartment, rendering it a most relevant model to investigate and target myeloid cells in immunotherapy. As innate immunity has been shown to be involved in many pathologies, BRGSF-HIS mice could prove helpful and pertinent, not only in oncology but in auto-immunity, inflammation, and many more applications.
- Teige I, Mårtensson L, Frendéus BL. Targeting the Antibody Checkpoints to Enhance Cancer Immunotherapy-Focus on FcγRIIB. Front Immunol. 2019 Mar 12;10:481.
- Fournier N, Jacque E, Fontayne A, Derache D, Dupont G, Verhaeghe L, Baptista L, Dehenne A, Dezetter AS, Terrier A, Longue A, Pochet-Beghin V, Beghin C, Chtourou S, de Romeuf C. Improved in vitro and in vivo activity against CD303-expressing targets of the chimeric 122A2 antibody selected for specific glycosylation pattern. MAbs. 2018 May/Jun;10(4):651-663.