On November 10, 2022 Imugene Limited (ASX:IMU), a clinical stage immuno-oncology company and Celularity Inc. (Nasdaq: CELU) (Celularity), a clinical-stage biotechnology company developing placental-derived allogeneic cell therapies and biomaterial products, reported that data from preclinical studies of Imugene’s onCARlytics (CF33-CD19) oncolytic virus in combination with Celularity’s placental-derived off-the-shelf allogeneic CYCART-19 T cells was presented at the renowned Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), held in Boston, USA on 8-12 November 2022 (Press release, Imugene, NOV 10, 2022, View Source [SID1234623879]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Dr Anthony Park from Dr Saul Priceman’s lab at City of Hope presented the poster, "CF33-CD19t oncolytic virus (onCARlytics) in combination with off-the-shelf allogeneic CYCART-19 T-cells targeting de novo CD19t expressing tumors."
Key findings of the presentation are as follows:
onCARlytics can target triple-negative breast cancer cell line MDA-MB-468 to express CD19t as a CAR T cell target in a virus dose-dependent manner.
CYCART-19 demonstrated efficacy in preclinical models against MDA-MB-468 expressing CD19t following onCARlytics infection.
There was an increase in CYCART-19 activation and IL-2 production in a virus dose-dependent manner.
Allogeneic CYCART-19 T cells produced less IFN-γ compared to autologous CD19-CAR T cells after CD19t-expressing tumor killing.
CD19t expression was detected in tumors following onCARlytics infection in vivo.
CYCART-19 treatment 7 days post onCARlytics infection showed significant tumor regression compared to onCARlytics or T cells alone in a mouse xenograft model of triple-negative breast cancer.
The poster is available on Imugene’s website, View Source and Celularity’s website, View Source
Imugene CEO/MD Leslie Chong said "When we embarked on the partnership with Celularity we were eager to investigate the combination of the cutting-edge technologies, Imugene’s onCARlytics and Celularity’s placental-derived allogeneic CAR-T (CYCART-19). The results presented at SITC (Free SITC Whitepaper) further build our confidence as to the potential benefit to patients from these technologies and provide an excellent platform for further clinical development."
Celularity Founder, Chairman and CEO Bob Hariri added, "We are encouraged by the potent cytolytic activity observed in the CYCART-19 preclinical models when combining Imugene’s onCARlytics product with our placentally derived CYCART-19 cells. The cytokine secretion profile demonstrated by the CYCART-19 cells suggests this combination may elicit reduced CRS potential in patients compared to PBMC derived CAR-T products."
About CYCART-19 T cells combination with onCARlytics
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 responses in solid tumors, including limited tumor-restricted CAR targets and the immunosuppressive tumor microenvironment. We have recently reported the successful combination immunotherapy using a novel chimeric vaccinia-based oncolytic virus (OV), called onCARlytics (Imugene Limited) that is engineered to express a non-signaling truncated CD19 (CD19t) antigen for tumor-selective delivery, enabling de novo targeting of tumor cells by autologous CD19-CAR T cell1. One of the field’s unanswered questions is whether treatment-naïve allogeneic CAR T cells are superior to cancer patient-derived T cells for product manufacturing to improve overall responses against solid tumors.
This combination strategy was evaluated using two allogeneic CAR T cell products generated from peripheral blood mononuclear cells (PBMC) and placental T cells, respectively. PBMC-derived CAR T cells were manufactured from normal healthy donors. CYCART-19 (Celularity Inc.) cells were derived from postpartum human placental T cells that are genetically modified to express the CD19 CAR followed by CRISPR-Cas9-mediated knockout of the endogenous t cell receptor (TCR) and expanded to produce multiple doses of allogeneic "off-the-shelf" treatment.
CYCART-19 T cells induced potent cytolytic activity against solid tumor cells infected with onCARlytics. Interestingly, while we observed comparable anti-tumor activity between PBMC-derived CD19-CAR T cells and CYCART-19, differences in cytokine secretion were detected. This warrants the possibility that the placenta-derived CAR T product may elicit reduced cytokine release syndrome (CRS) potential in patients with maintained or improved efficacy. This combination approach demonstrated in vivo anti-tumor response in human tumor xenograft models. In summary, our results have demonstrated that further development of this combination immunotherapy for the potential treatment of a wide array of solid tumors is warranted.
References
¹ Warner SG, Kim SI, Chaurasiya S, O’Leary MP, Lu J, Sivanandam V, Woo Y, Chen NG, Fong Y. A Novel Chimeric Poxvirus Encoding hNIS Is Tumor-Tropic, Imageable, and Synergistic with Radioiodine to Sustain Colon Cancer Regression. Mol Ther Oncolytics. 2019 Apr 11;13:82-92. doi: 10.1016/j.omto.2019.04.001. PMID: 31061881; PMCID: PMC6495072.