9P - An in vivo model for therapeutic antibody efficacy evaluation: The chicken embryo’s CAM-based assay

Background

Since its introduction, xenografts on the chicken embryo’s ChorioAllantoic Membrane (CAM) has been proven extremely valuable for in vivo studies in cancerology. It is suitable to study tumor development, angiogenesis, malignant cell dissemination, chemotherapy efficacy and toxicity. Here, we demonstrate that this in ovo model, which has an active immune system, is useful for rapidly testing and comparing the efficacy of therapeutic antibodies, like anti-PD1/PD-L1 Abs, Antibody-drug Conjugates (ADCs), etc., on tumor growth and metastatic invasion.

Methods

Tumor cells are grafted on the CAM of chicken egg on day 9 of development. After engraftment, tumors are treated with therapeutic antibodies for 8 days, from a single injection for ADCs, to the treatment every other day for other types of antibodies. Maximal tested doses are scaled to the dose used in murine immune deficient models and in human (in mg/kg). Antibodies validated in ovo are FDA approved antibodies, against antigens expressed by tumor cells or immune cells, like immune checkpoint inhibitors (anti PD1/PD-L1 Abs) or ADCs (T-DM1).

Results

After treatment, the toxicity and the efficacy of tested Abs are analyzed and compared to non-treated control. The table presents the effect of antibodies on tumor growth in the CAM assay. A single antibody leads to different efficacy levels in function of the cancer types. Ab’s efficacy is also checked by measuring metastatic invasion in lower CAM (far from the tumor) and in embryonic tissues, immune cell infiltration or angiogenesis development. Deeper analysis can be performed, like transcriptomic analysis on the tumor to characterize mechanisms of action or more specific and/or fine effects on tumor cell physiology. Table: 9P

Effect of antibody therapies on tumor weight in ovo

Conclusions

Here we demonstrate that the CAM model is suitable to test therapeutic antibodies, immune therapies and ADCs in vivo. The presence of an active immune system allows to characterize of the effect of antibodies on tumor cell, microenvironment and the entire organism.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Inovotion.

Funding

Inovotion.

Disclosure

All authors have declared no conflicts of interest.