Spotlight on our syngeneic MCA205 tumor model: A reliable tool to investigate novel therapy combination
06 / 01 / 2021
Current immunotherapies, especially immune checkpoint inhibitors such as PD1 / PDL1 axis blockers (Nivolumab, Pembrolizumab, Atezolizumab, etc.), have dramatically changed the clinical outcome of cancer patients and constitute now an important part of the therapeutic armamentarium. However, despite their success, the benefit of cancer immunotherapies remains limited to a fraction of patients and varies according to the tumor histotype as well as with the intrinsic features of the tumor (eg. Tumor Mutational Burden, PDL1 expression, etc.) or its microenvironment (immune cell infiltration, fibroblast abundance, etc.). As to increase the current rate of response, several approaches are under evaluation and include combination therapies targeting other immune checkpoints (CTLA4, TIGIT, LAG3, etc.), or immunosuppressive pathways (Adenosine, Kynurenine, Arginine, etc.), etc.
Using a syngeneic MCA205 sarcoma tumor model – widely used for the evaluation of innovative cancer immunotherapies – we investigated the anti-tumor activity of several combination therapies. This model is known to be responsive to PD1/PDL1 axis blockade but only partially to anti-CTLA4 antibody. Interestingly, while an additive benefit of anti-PD1 and anti-PDL1 is observed, a clear synergistic effect is achieved upon combination of either anti-PD1 or anti-PDL1 with anti-CTLA4, with a full tumor rejection in all treated animals.
These data highlight the suitability and relevance of our robust MCA205 mouse tumor model to assess novel combinatorial strategies – on top of benchmark therapeutics - for their potential synergistic effect, which can ultimately be deciphered through multiple ancillary approaches (tumor immune cell infiltrate and gene expression analysis, digital pathology, etc).