Combinatorial Therapy of Il-21 Secretion Oncolytic Virus and Anti-Ror1 Car Nk Cells Against Ne: Significant Effect In-Vitro and In-Vivouroblastoma
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
2022
DOI
10.1002/pbc.29952
Journal Title
Pediatric Blood and Cancer
Department
Pediatrics
Abstract
Background and Aims: Novel therapies are desperately needed for children with recurrent and/or metastatic neuroblastoma (NB) (Chu/Cairo, JITC, 2021). ROR1 is highly expressed by most NB. Our group has successfully expanded peripheral blood NK cells (exPBNKs) with feeder cells and electroporated CAR mRNA to exPBNKs (Chu/Cairo, Cancer Immunol Res, 2015). Oncolytic herpes simplex viruses (oHSVs) have been safely used in clinical trials for a wide range of cancers (Cassady, et al, JITC, 2021). We sought to determine the anti-tumor efficacy of the therapy combination of oHSV engineered to express human IL21 with anti-ROR1 CAR engineered exPBNK cells (CAR exPBNKs) against ROR1+ NB. Methods: ExPBNKs were expanded and electroporated with antiROR1-CAR mRNA (Chu/Cairo, JITC, 2021). oHSV C134 was modified to express hIL-21 gene (C021). The supernatants containing C134 and C021 were generated as previously described (Cassady, et al, JITC, 2021). In-vitro cytotoxicity of CAR exPBNKs against NB cell lines were examined by ELISA assays of IFN-g, granzyme and perforin levels. Invivo hIL21 secretion and anti-tumor effect of the C021 with CAR exPBNKs was examined utilizing human NB xenografted NSG mice. Results: C021 at MOI 0.025 or CAR exPBNKs significantly inhibited NB growth compared to controls. The combination of C021 and CAR exPBNKs significantly enhanced the killing of NB (p<0.05) with significantly enhanced secretion of IFN-g (p<0.05), granzyme B (p<0.05) and perforin (p<0.05) and significantly enhanced expression of NK activating marker CD25 (p<0.05) compared to controls. Our in-vivo animal study showed that NB infected with C021 secreted hIL21 and the combination of C021 and CAR exPBNKs reduced tumor burden in human NB xenografted NSG mice compared to the untreated group (p<0.05) and the CAR exPBNKs-treated group (P=0.056). Conclusions: Our data demonstrate the significant anti-tumor efficacy of combining C021 with anti-ROR1 CAR exPBNKs to therapeutically target NB in-vitro and in-vivo.
Recommended Citation
Chu, Y., Tian, M., Saini, U., Cripe, T., Mardis, E., Lee, D., Riddell, S., Cassady, K., & Cairo, M. (2022). Combinatorial Therapy of Il-21 Secretion Oncolytic Virus and Anti-Ror1 Car Nk Cells Against Ne: Significant Effect In-Vitro and In-Vivouroblastoma. Pediatric Blood and Cancer, 69, S213-S214. https://doi.org/10.1002/pbc.29952
