Charles River is establishing a powerful translational immuno-oncology platform with the capability of progressing biologics or small molecule modulators of immune response from in vitro to in vivo assays using human and mouse variants of current check-point inhibitors and small molecules.
The platform includes validated (using chemotherapeutics, including anti-CTLA4, anti-PD1 and small molecule inhibitors of targets known to modulate immune responses including IDO inhibitors) primary human immune cell assays which profile T cell activation, cytokine release, T cell mediated cancer cell kill, expansion of T cell populations, T cell invasion and macrophage mediated T cell phagocytosis and is currently being expanded to determine the effect of activated immune cell populations on tumour cell spheroid cultures. We are in the process of developing a range of nuclear-restricted GFP expressing cell lines which will be used to support co-culture experiment.
Syngeneic mouse tumour models have frequently been used to profile immune responses in tumours, CRL have optimized and profiled existing check-point inhibitors to support immuno-oncology drug discovery using mouse and rat antibody variants of anti-CTLA4 and anti-PD1.
To confirm the translational development of our platform CRL have developed and optimized humanized mouse models using sub-cutaneous implanted patient derived xenografts (PDX) with human engraftment via CD34+ haematopoeitic stem cells in NOG mice which were treated with anti-CTLA4 and anti-PD1. Infiltration of human immune cells and PDL-1 expression was detected by flow cytometry (FC) and immunohistochemistry (IHC) in hematopoietic organs and tumor tissue, supporting the initial in vitro response in primary immune cells.
Shilina Roman– Charles River
Gary Salmon– Charles River
Julie Hawkins– Charles River
Jonathan White– Charles River
Ria Goodwin– Charles River
Runi Ganguli– Charles River
Omar Aziz– Charles River
Julia Schueler– Charles River
Edgar Wood– Snr. Research Director, Charles River
Jeroen DeGroot– Senior Director, Charles River Laboratories
Ian Waddell– Charles River