Tumor RNAseq and nCounter for ERY974 monotherapy and/or combination with chemotherapy

We examined pharmacodynamic (PD) of ERY974, CD3 and GPC3-targeting T cell
bispecific antibody (TRAB), in tumors of huminized/NOG mice administered
with ERY974 and/or chemotherapy. First, we examined the RNAsea data of
ERY974 monothrapy for tumors of PC10, NCI-H446, MKN45, and MKN74 of
humanized/NOG mice. We found that gene expression related with immune
cells at baseline is correlated with efficacy of ERY974. Then,we examined
the PD of ERY974 combined with chemotherapy (paclitaxel, cisplatin and
capecitabine). In NCI-H446, a representative of non-inflamed-tumor, we
examined the tumor RNA of huminized/NOG mice administered with ERY974
and/or paclitaxel, or cisplatin. In MKN45, a representative of
non-inflamed-tumor, we examined the tumor RNA of huminized/NOG mice
administered with ERY974 and/or capecitabine. For capecitabine
combination, we firstly examined the suitable timing among day 3,7,and 14
when combination effect was cleary observed, and found that day 14 is the
most suitable timing. From all the data, we found that combination of
chemotherpay increased ERY974-induced gene expression related with T cell
marker and T cell activation. To examine if our findings  are
observed in other TRABs in common, we parepred for the EGFR-TRAB, and
examined the RNA analysis of MKN45 tumor of huminized/NOG mice administred
with EGFR-TRAB and/or paclitaxel. We confirmed that paclitaxel increased
EGFR-TRAB-induced gene expression related with T cell marker and T cell
activation. We concluded that combination of TRABs with chemotharpy is
suitable strategy to erradicate non-inflamed tumors.