Fig. 7: Low dose BiA9*2_HF loaded with tagged E7 derived tumor antigen induces anti-tumor responses on distant growing TC-1 tumor with minimal toxicity effects. | Nature Communications

Fig. 7: Low dose BiA9*2_HF loaded with tagged E7 derived tumor antigen induces anti-tumor responses on distant growing TC-1 tumor with minimal toxicity effects.

From: A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice

Fig. 7

A Tumor volume over time and survival analysis in mice treated with indicating groups using 30 µg (150pmol) of BiA9*2_HF and 3 µg (925 pmol) of E744-62 peptide with and without pTag in the TC-1 model. Tumor growth: E744-62 n = 6, BiA9*2_HF n = 6, BiA9*2_HF + E744-62 n = 6, BiA9*2_HF + pTag9aa-E744-62 n = 8, tgCD40 from Biocytogen. *p = 0.0112, calculated with the Kruskal-Wallis test with Dunn’s multiple comparisons test. Survival analysis: E744-62 n = 6, BiA9*2_HF n = 5, BiA9*2_HF + E744-62 n = 5, BiA9*2_HF + pTag9aa-E744-62 n = 7, tgCD40 from Biocytogen. **p = 0.0018 calculated with Kaplan-Meier survival analysis with log-rank test. B Survival analysis of mice over time treated in the indicating groups using 30 µg of BiA9*2_HF and 1.5 µg (450 pmol) of E744-62 peptide linked to the pTag injected s.c or 100 µg intravenously infused selicrelumab. Vehicle n = 4, selicrelumab n = 3, BiA9*2_HF + pTag9aa-E744-62 n = 7, tgCD40 from Biocytogen. *p = 0.0296 calculated with Kaplan-Meier survival analysis with log-rank test. C Tetramer positive antigen-specific CD8+ T cells in circulating blood of treated mice performed at day 17. Vehicle n = 5, selicrelumab n = 3, BiA9*2_HF + pTag9aa-E744-62 n = 4. The whiskers show min and max values, and the box extends from 25 to 75 percentiles, with the middle line representing the median. *p = 0.0488 and calculated with one-way ANOVA with Dunnett’s multiple comparison test. D AST levels in plasma 24 h post first treatment with indicated groups, same mol ratio between the i.v doses. D Vehicle n = 5, selicrelumab n = 5, BiA9*2_HF i.v n = 5, BiA9*2_HF + pTag9aa-E744-62 s.c n = 5, tgCD40 from Biocytogen. P-values are shown in the graph and calculated with the Kruskal-Wallis test with Dunn’s multiple comparison test. E Platelet counts after 4 h in ID. Flow. Graph shows fold change of platelets (PLTs), presented as percentage change as compared to test buffer alone. BiA9*2_HF+pTag9aa-KRASG12D n = 10 and selicrelumab n = 10. **p = 0.0021 calculated with unpaired Mann-Whitney t test. F, G Quantified levels of ALT and ALP in plasma of immunized NHPs with BiA9*2_HF and pTag9aa-KRASG12V at indicated time-points. Arrows indicate the time of vaccination, and * indicates that only NHP-II got the third treatment.

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