Similar to the 4T1 tumor model, combination treatment significantly reduced tumor growth in comparison to the single treatments although treatment was started after the initiation of tumor growth (Figure 7A).
In the latter model, combination treatment resulted in an increased infiltration of both innate (CD11c dendritic cells, CD11b + myeloid cells, NK, and NK T cells) and adaptive (CD4+ and CD8+ T cells) tumor-infiltrating immune cells.
In a pre-clinical B16F10 mouse melanoma model, a combination treatment with anti-CD4+ and anti 4-1BB monoclonantibodiesies potentiated the observed anti-cancer effects [ 63].
In addition, in the intracranial model, the combination treatment was more efficacious, resulting in a 73% decrease in tumour volume 25 days after the start of therapy, as well as in a longer survival of the animals.
Mumenthaler, S.M*., Foo, J*., Leder, K., Choi, N.C., Agus, D.B., Pao, W., Mallick, P. & Michor, F. Evolutionary modeling of combination treatment strategies to overcome resistance to tyrosine kinase inhibitors in non-small cell lung cancer.
We will model this phenomenon by using an extension of the stochastic model for combination treatments with cross-resistance, first introduced in [59], [60].
In this work we have proposed a mathematical model for the combination treatment of chronic myelogenous leukemia with imatinib and IFN-α to overcome immune suppressive side effects of imatinib, prolonging the chronic phase of the disease.
Finally, analysis of the combination in an MV4-11 mouse xenograft model demonstrated that combination treatment significantly reduced tumour growth compared with the single-agent treatments, confirming that the combination was an effective in vivo therapeutic option.
The combinatorial anti-tumor effects of anti-HER2 and anti-PD1 demonstrated in experimental models are important proof-of-principle experiments that the anti-tumor adaptive immunity provoked by anti-HER2 can be capitalized upon, providing a new model of potential combination treatment for women receiving trastuzumab.
These data inspired us to revisit our modeling of combination treatments with a different approach.
Dual immunotherapy via B cell depletion and BAFF blockade is more efficacious than single agent immunotherapy in murine SLE models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human SLE.
