Poly(L-glutamic acid) based composites for improved dual immune checkpoint blockade therapy

Abstract The immune checkpoint blockade (ICB) therapy, such as PD1/PDL1 blockade, is successful for robusting the duable response of patients. However, the response rate is less than 30%. In this study, we prepared polymer-Fc binding peptides-based PD1/PDL1 bispecific antibody (BsAb), which was constructed via the condensation reaction between side –COOH of poly(L-glutamic acid) (PGLU) and –NH2 of a double cyclic peptide Fc-III-4C, and mixed with αPD1 and αPDL1 monoclonal antibodies (mAbs) in an aqueous solution. The PD1/PDL1 BsAb forms a bridge between tumor cells and CD8+ T cells, persistently activating the CD8+ T cell to a greater degree, and results in a much stronger inhiation of tumor growth and a longer survival time of mice in mouse colon cancer model, than both the free mAb and free mixed mAbs. The tumor suppression rate of the BsAb was 90.1% and after 48 days, the survival rate is 83.3%. Thus, this study highlights an effective PD1/PDL1 BsAb synchronizing T cell engager and dual ICBs, facilitating and guiding theoretically the clinical ICB therapy.