ErbB2-CAR mediated immunotherapy for the treatment of high-risk rhabdomyosarcoma

Metastatic rhabdomyosarcoma (RMS) is a tumor entity with unmet need for novel treatment strategies. Applying the chimeric antigen receptor (CAR) technology to innate immune cells may translate into effective, safe and affordable therapies that contribute to cancer immune surveillance not only by their intrinsic cytotoxicity, but also by modulating antitumor immune responses.

CAR-engineered natural killer cell line NK-92/5.28.z directed against ErbB2 on RMS displayed effective cytotoxicity against primary RMS in vitro. Even if kept under hypoxic conditions of tumor spheroids, NK-92/5.28.z was able to overcome effects of the inhibitory tumor microenvironment. In mice carrying a patient’s tumor-derived RMS xenografts, serial infusions of NK-92/5.28.z delayed tumor engraftment, whereas one systemic application of ex vivo activated ErbB2-CAR-engineered cytokine induced killer (CIK) cells inhibited tumor growth, suggesting that the selection of the immune effector cell is critical for CAR therapy.

For clinical application, we are now continuing with early treatment attempts in vitro using the novel Sleeping Beauty transposon-based system (SBTS) for CAR gene transfer in CIK cells.

Publikationsverlauf

Artikel online veröffentlicht:
17. Mai 2022