Multiple signaling pathways are usually involved in the development of
tumors. Compared with monospecific
antibodies, bispecific antibodies can recognize two different
antigens at the same time, so they are more suitable for treating
tumor diseases with complex etiology.
Immunotoxins have good antitumor activity, however, single targeting limits their effectiveness. Herein, we designed a Pseudomonas
exotoxin A (PE)-based bispecific
immunotoxin IgBD-HER2-PDGFRβ-PE38 which could distinguish HER2 and PDGFRβ target in
tumor. Meanwhile,
IgG-affinity could extend the serum retention of
immunotoxins after in vivo injection. In this work, we first detected the selective binding of the
immunotoxins and antitumor effect in vitro. Compared with control group, IgBD-HER2-PDGFRβ-PE38 exhibited improved efficacy against HER2-positive
tumors in an NCI-N87 subcutaneous xenograft model. Then, transcriptome sequencing was performed on
tumor tissue originating from different treatment groups of mice bearing NCI-N87
tumors. Seven significantly differentially expressed genes were screened based on human genes, and the differential mouse genes were enriched based on the Reactome Pathway Database. At last, the
RNA sequencing results were verified by real-time PCR and ELISA. Therefore, the new construct bispecific
immunotoxin represents a potentially attractive therapeutic modality, and the proposed strategy make them promising for use in the development of anti-HER2
cancer therapeutics.