Improving NK-cell immunotherapy against rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in children and although the survival rate has increased over the last decades the outcome of patients with metastatic and relapsed disease is still poor.

Natural killer (NK) cells are known for their high intrinsic cytotoxic capacity and can be safely applied as ‘off-the-shelf’ third party donor product. Chimeric antigen receptor (CAR)-expressing NK cells showed promise for the treatment of B-cell malignancies, while so far only limited data exist for solid tumor therapy.

We addressed relevant pathways in the peripheral blood derived NK (pNK)-RMS interaction by RNA sequencing analysis, RT-qPCR and CRISPR/Cas9-knockouts in NK or RMS cells. pNK cells that were rechallenged with RMS spheroids after RMS contact showed reduced cytotoxicity, indicating that the NK-RMS interaction impaired pNK antitumor activity.

To enable more specific targeting and enhance NK-cell cytotoxicity, we generated pNK cells equipped with a CAR targeting the epidermal growth factor receptor (EGFR). These EGFR-CAR NK cells showed increased cytotoxicity against various RMS cell lines. In vivo analysis in an RMS mouse xenograft model is ongoing.

Publication History

Article published online:
17 May 2022