Journal
TRANSLATIONAL ONCOLOGY
Volume 14, Issue 1, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2020.100916
Keywords
Bispecific antibody; PD1; EGFR; Immune checkpoint blockade; Targeted therapy
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Funding
- Pujiang Talent Program of Science and Technology Commission Shanghai Municipality [19PJ1430800]
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The study developed a new strategy by combining conventional targeted therapy with immune checkpoint blockade using a tumor-targeting bispecific antibody. This antibody not only directly inhibits tumor growth through EGFR inhibition but also activates T cell anti-tumor immunity by blocking the interaction between PD1 and PDL1.
We developed a strategy to combine conventional targeted therapy with immune checkpoint blockade using a tumor-targeting bispecific antibody (BsAb) to treat solid tumors. The BsAb was designed to simultaneously engage a tumor-associated antigen, epidermal growth factor receptor (EGFR), and programed cell death protein 1 (PD1). In addition to its direct anti-tumor activity via EGFR inhibition, the BsAb mediated efficient antibody-dependent cellular cytotoxicity (ADCC) and activated T cell antitumor immunity through blockade of PD1 from interacting with its counterpart, programed cell death ligand 1 (PDL1). Further, the BsAb exhibited a potent direct tumor cell killing activity in the presence of PBMC, most likely, via activating and, at the same time, physically engaging T cells with tumor cells. Taken together, we here illustrate a new strategy in the design and production of novel BsAbs with enhanced therapeutic efficacy through both direct tumor growth inhibition and T cell activation via tumor-targeted immune checkpoint blockade.
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