GD2 or HER2 targeting T cell engaging bispecific antibodies to treat osteosarcoma.

ABSTRACT:

Background

The cure rate for metastatic osteosarcoma has not substantially improved over the past decades. Clinical trials of anti-HER2 trastuzumab or anti-GD2 dinutuximab for metastatic or refractory osteosarcoma were not successful, and neither was immune checkpoint inhibitors (ICIs).

Methods

We tested various target antigen expressions on osteosarcoma cell lines using flow cytometry and analyzed in vitro T cell engaging BsAb (T-BsAb)-dependent T cell-mediated cytotoxicity using 4-h ⁵¹Cr release assay. We tested in vivo anti-tumor activities of T-BsAb targeting GD2 or HER2 in established osteosarcoma cell line or patient-derived xenograft (PDX) mouse models carried out in BALB-Rag2^-/-IL-2R-γc-KO (BRG) mice. We also generated ex vivo BsAb-armed T cells

SUBMITTER: Park JA 

PROVIDER: S-EPMC7731630 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature