In Vitro Functional Bioassays of Candidate Therapeutics in Immuno-Oncology
Juliette Lamy1, Brecht Hoedemaekers1, Séverine Giltaire1, Sofie Pattijn1
1ImmunXperts SA, rue Auguste Piccard 48, 6041 Gosselies, Belgium
The observation showing the immune suppression induced in the tumour microenvironment increases the development of immunotherapies in cancer. In the past few years, new cancer treatments based on immunology 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) or antigen-specific recall activation assay with human T cells are models that mimic a physiological T cell response. These kinds of assays can be used to screen 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 MLR in the presence of tumour cells or the study of Tumour Associated Macrophages (TAM). These are new assays to screen the effectiveness of new therapeutics in vitro.
For example, the analysis of macrophages polarization or M2-macrophages suppression of T cells 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 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 dendritic cells which are co-cultured with allogenic T cells. Response levels can be evaluated by the assessment of proliferation or measurement of cytokine production.