Human responses against HER-2-positive cancer cells in human immune system-engrafted mice

Autor: E. Barbieri, R. M. Lemoli, Pier Luigi Lollini, Valeria Stivani, Stefania Croci, F. Romani, C. De Giovanni, Manuela Iezzi, Agnese Antognoli, Annalisa Murgo, Arianna Palladini, Marianna L. Ianzano, Lorenzo Stramucci, Lorena Landuzzi, Patrizia Nanni, Valentina Grosso, Giordano Nicoletti
Přispěvatelé: De Giovanni C., Nicoletti G., Landuzzi L., Romani F., Croci S., Palladini A., Murgo A., Antognoli A., Ianzano M.L., Stivani V., Grosso V., Iezzi M., Stramucci L., Barbieri E., Lemoli R.M., Nanni P., Lollini P.L.
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: British Journal of Cancer
Popis: Attempts to obtain mice reconstituted with a human immune system (HIS) mice, also referred to as HIS mice, date back to the end of 1980s, when mice carrying the Prkdcscid mutation were first used as recipients of human progenitors, with limited success (Shultz et al, 2007). In the last decade, mice with engineered combined immunodeficiencies were obtained and a more efficient engraftment of human hematopoietic stem cells (HSC) was described (Shultz et al, 2007; Manz and Di Santo, 2009; Brehm et al, 2010). Even though the full human reconstitution is generally not achieved, HIS mice have already given valuable results for a better understanding of the differentiation potential of human immune populations (Huntington and Di Santo, 2008; Meek et al, 2010) and for the study of viral human pathogens (Legrand et al, 2009). Moreover, HIS mice are interesting models for human vaccine development (Koo et al, 2009; Becker et al, 2010). Human immune system mice, could provide new experimental models to study the relationships between human tumours and human immune effectors (Brehm et al, 2010; Wege et al, 2011). BALB/c Rag2−/−;Il2rg−/− (hereafter referred to as BRG mice), display a severe combined immunodeficiency, with absence of T, B and NK cells (Nomura et al, 2008). These mice can unveal growth and metastatic ability of human xenografts, otherwise not apparent in mice with partial immunodeficiencies (Nanni et al, 2010). BALB/c Rag2−/−;Il2rg−/− mice have been effectively used to obtain HIS mice (Traggiai et al, 2004; Brehm et al, 2010) and to test antitumour activity of human immune effectors (Thiel et al, 2011). We exploited these features to study the possibility to induce immune responses against human cancer cells by human lymphocytes and their ability to control tumour growth and metastasis. As the tumoural counterpart, we selected a HER-2-positive human cancer cell line. Therapeutic targeting of HER-2-overexpressing cancers with the humanised monoclonal antibody trastuzumab has already entered the clinical practice, but the search for active immunisation strategies against HER-2 is also pursued (Wei et al, 2008). In transgenic models of HER-2-driven mammary carcinogenesis, immune targeting of HER-2 with both active and passive approaches has shown preventive and therapeutic activity (Lollini et al, 2011). Transgenic models are suitable to study, at best, the murine immune response against the transgenic human HER-2 molecule, but cellular or soluble immune effectors elicited in transgenic mice are not of human origin. In the first part of this study we investigated the reconstituting ability of two types of HSC sorted from human cord blood: CD34+ and CD133+ cells. CD34+ progenitors have been extensively used to obtain HIS mice, see for BRG the pioneering study of Traggiai et al (2004). CD133+ HSC engraftment was reported after in vitro culture in growth factor-supplemented medium (Drake et al, 2011), whereas studies with freshly isolated CD133+ HSC in BRG mice and a direct comparison with CD34+ HSC engraftment ability have not been reported. Subsequently, we investigated the ability to elicit an immune response against HER-2-positive human cancer cells.
Databáze: OpenAIRE
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