In vivo anti-tumor effects of XON7 in association with ICIs

e14520 Background: The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm for multiple cancer types. This remarkable shift has been driven in large part by unprecedented durability that is characteristic of ICIs responsiveness. However, ICIs promote tumor cell immune escape; indeed, the response rate to single agent PD-1 blockade in unselected patients ranges from 40 to 70% in some diseases, while the response rates in most other approved diseases is limited to 10–25%. These observations support the need to strengthen immunotherapy and bring additional benefits for patients. XON7, is a glyco-humanized polyclonal antibody (GH-pAb) targeting multiple tumor antigens and active in vitro and in vivo in several solid tumors and hematological malignancies. Methods: A human lung carcinoma chorio-allantoic membrane (CAM) model was used to evaluate the efficacy of XON7 + anti PD-1 treatment. Fertilized white Leghorn eggs were incubated until Day 9, then inoculated in the upper CAM with 1.10 6 H460 cells. Treatments were administrated at E10, E12, E14, E15 and E17. Two groups were included: control group (n=20) received a non-immune GH-pAb + anti-PD-1 (10 mg/kg + 2,5 mg/kg respectively); treated group (n=20) received XON7 and anti-PD-1 at the same doses. Upper CAM, lower CAM and brain were collected from the embryos at E18. Tumor growth was evaluated by tumor weight using one-way ANOVA. Metastasis were quantified by qPCR for Alu sequences. Immune cell infiltration was analyzed by RT-qPCR with specific primers for chicken CD3, CD4 and CD8 sequences, with GAPDH as reference gene expression. Results: Significant reduction in tumor growth (~30%, p=0.02) and metastasis (>90%, p=0.001) was observed in both the brain and the lower CAM in the XON7+ICI group compared to control group. No differences in lymphocyte infiltrates (CD3, CD4, and CD8) were observed between groups. However, a significant increase in the M1/M2 ratio was observed in the XON7 + anti-PD-1 group over control. No toxicity from the treatment appeared in this model. Conclusions: In vivo data showed a significant increase of response rate and decrease of metastasis when XON7 is associated with anti PD-1. Combination of GH-pAb with ICI could constitute an immunotherapy combination likely to overcome resistance to anti-PD1.