In Vitro Functional Bioassays of Candidate Therapeutics in Immuno-Oncology Thibaut Janss1, Juliette Lamy1, Thibault Jonckheere1, Séverine Giltaire1, Sofie Pattijn1 1ImmunXperts SA, rue Auguste Piccard 48, 6041 Gosselies, Belgium
The observation showing the immune suppression induced in the tumour microenvironment was the basis for the development of immunotherapies in cancer. During the last decade, new cancer treatments aiming to support and boost the patient's immune system such as CTLA-4 or PD-1 blockade open new roads to targeted treatments to reverse the tumour-induced immunosuppression.
In vitro bioassays can be developed to analyse the effect of new candidate therapeutics on immune cells. Mixed lymphocyte Reaction (MLR), antigen-specific recall activation assay or CD3/CD28 activation assays with human T cells are models that mimic a physiological T cell responses. These kinds of assays can be used in the development phase to screen the functionality of new candidate therapeutics such as immune checkpoint blocking antibodies. Recently the increasing interest in the tumour microenvironment leads to focus on new bioassays to represent all the players of the cancer immune response like T cell activation assays in the presence of tumour cells, myeloid derived suppressor cells (MDSC) or regulatory T cells (Treg) or the study of Tumour Associated Macrophages (TAM).
The analysis of macrophage polarization or M2-macrophage suppression of T cell proliferation in the presence of candidate therapeutics can be done in vitro starting from human monocytes to evaluate the potential capacity of therapeutics to promote M1 re-polarization of TAM.
An important factor for sensitive and reproducible assays and consistent results is the quality of the primary immune cells. PBMC are isolated and cryopreserved shortly after blood redrawn. All donor preparations are quality controlled and HLA typed and optimized procedures are used to generate functional subpopulations such as dendritic cells and T cell subpopulations. Next to that, in vitro assays need to be optimised and fine-tuned for the screening of certain types of molecules and the use of different specific subpopulations of immune cells.