847 CF33-CD19t oncolytic virus (onCARlytics) in combination with off-the-shelf allogeneic CyCART-19 T cells targeting de novo CD19+ solid tumors

• DOI: 10.1136/jitc-2022-sitc2022.0847
• Publication Date: 2022-11-08T01:11:06Z
• Authors: Anthony Park; Isabel Monroy; Colin Cook; Shuyang He; Kathy Karasiewicz; Monil Shah; Nimali Withana; Leslie Chong; Robert Hariri; Yuman Fong; Saul Priceman
• Keywords: Cell therapy; Cancer Immunotherapy

<h3>Background</h3> Autologous chimeric antigen receptor (CAR) T cell therapy has shown impressive clinical responses against CD19+ B-cell hematological malignancies and is being actively explored in the treatment of solid tumors. However, several barriers have precluded therapeutic tumors, including limited tumor-restricted CAR targets immunosuppressive tumor microenvironment. We recently reported successful combination immunotherapy using a novel vaccinia-based oncolytic virus (OV), called onCARlytics (Imugene Limited), that engineered to express non-signaling, truncated CD19 (CD19t) for tumor-selective delivery, enabling de novo targeting cells by autologous CD19-CAR cells. One field's unanswered questions whether treatment-naïve allogeneic are superior cancer patient-derived product manufacturing improve overall <h3>Methods</h3> Here, we evaluated this strategy two products generated from peripheral blood mononuclear (PBMC) placental cells, respectively. PBMC-derived CAR-T were manufactured normal, healthy donors. CYCART-19 (Celularity, Inc.) derived postpartum human genetically modified followed CRISPR-Cas9- mediated knockout endogenous TCR expanded produce multiple doses "off shelf" treatment. For preclinical testing, utilized <i>in vitro</i> co-culture assays. killing activation flow cytometry cytokine Xenograft mouse models used evaluate anti-tumor activity vivo</i>. <h3>Results</h3> induced potent cytolytic infected with onCARlytics. Interestingly, while observed comparable between CYCART-19, significant differences secretion detected. This warrants possibility placental-derived may elicit reduced CRS potential patients maintained or improved efficacy. approach demonstrated vivo response xenograft models. <h3>Conclusions</h3> In summary, our results further development wide array tumors warranted.