Immunophenotyping to Evaluate Efficacy of Novel Immunotherapies

It is well-established that syngeneic mouse models represent a powerful tool to evaluate therapies that target the immune system. The key to understanding your immuno-modulatory compound’s efficacy is to work with well-characterised models, with known growth kinetics and/or response to standard of care treatments.

At InnoSer, we are experienced with validating our clients’ cell lines to help determine the optimal seeding cell densities to induce stable and progressive in vivo tumour growth.

Our immuno-oncology teams have validated multiple commonly available cell lines such as metastatic breast cancer (4T1), pancreatic (Panc02), melanoma (B16F10) renal (Renca) and colorectal (MC38) carcinoma.

MC38 represents a common anti-PD-1-responsive tumour model. Disease progression is assessed via observation of clinical signs, body weight and tumour volume measurements. This model shows efficient growth kinetics and response to anti-PD-1 therapy (Left figure shows tumour volume measured by callipers, M ± SEM, **P<0.01, ***P<0.001) resulting in a model with a long dosing window to test novel immunotherapy candidates. InnoSer offers this both as a subcutaneous (MC38) and orthotopic (MC38-luc) model allowing bioluminescent imaging of tumour progression (Right image shows tumour progression in a subset of two mice).

Evaluating novel immunotherapies’ mechanisms of action can be complemented with extensive immune cell profiling, with custom-tailored panel establishment upon request.

Here, we performed immune cell profiling on colorectal carcinoma (MC38) tumours isolated from anti-PD-1 treated and vehicle-treated mice. Using panels for (A) myeloid cells and (B) lymphocyte cells, different cell populations can be distinguished including T cells (CD4+ vs. CD8+), B cells, monocytes, granulocytes and M1/M2 macrophages.  

Alternatively, tumour growth assessment can be also performed following subcutaneous flank injections of novel cell-based therapy products to monitor tumorigenicity as a side effect.