Clinical Potential of onCARlytics Under Exploration in Solid Tumors

Research in the solid tumors arena around the combination of the oncolytic virus technology CF33-CD19 and the CD19-targeting CAR placental-derived T-cell therapy CyCART-19, is underway to explore it’s potential in this patient population.

Research in the solid tumors arena around the combination of the oncolytic virus technology CF33-CD19 (onCARlytics) and the CD19-targeting CAR placental-derived T-cell therapy CyCART-19, is underway to explore it’s clinical potential in this patient population, according to an announcement from collaborators Imugene Ltd. and Celularity Inc.1

The clinical-stage immuno-oncology and biotechnology companies have partnered up to examine whether pairing their 2 platforms could help to overcome limitations that have hindered other existing methods. The strategy is to utilize an oncolytic virus to prime the tumor cells for destruction by eliciting CD19, which serves as a target for the CAR T-cell therapy.

“We are excited to initiate this research collaboration, which we believe will lay the foundation for a new approach to the treatment of solid tumors,” Robert J. Hariri, MD, PhD, founder, chairperson, and chief executive officer of Celularity, Inc. stated in a press release. “Most solid tumors have variable targetable antigens, limiting CAR T-cell therapy efficacy. This treatment strategy with Imugene has the potential to apply to a new range of indications by enabling CD19-targeted cellular medicine to expand from its current effective usage in CD19-positive lymphomas and leukemia and potentially become applicable to a variety of solid tumors through inducing uniform expression of CD19 in solid tumors.”

In May 2021, Imugene Ltd. entered into a licensing agreement with City of Hope for the patents covering the cell therapy technology platform, which includes CF33-CD19, an agent that had been developed at the institution.2

A scientific team led by Saul Priceman, PhD, an assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation, at City of Hope, engineered an oncolytic virus so that it would express a nonsignaling, truncated CD19 protein for tumor-selective delivery, which would enable CD19 targeting by CAR T cells.

Preclinical data published in the journal Scientific Translational Medicine indicated that infecting tumor cells with an oncolytic vaccinia virus that codes for truncated CD19 resulted in the production of de novo CD19 at the cell surface prior to virus-mediated tumor lysis.3 Moreover, cocultured CD19-targeted CAR T cells were found to secrete cytokines and showcase strong cytolytic activity in infected tumors. When OV19t and CD19-targeted CAR T cells were administered to mouse models, disease control was observed.

CyCART-19 is a placental-derived T-cell therapy that was developed with a CAR that is cryopreserved, allogeneic, and designed to be available as an off-the-shelf option.4 The therapy is under investigation as a potential option for patients with B-cell malignancies; it is designed to target the CD19 receptor.

Placental-derived T cells are mostly CD45RA+, readily expand ex vivo, and express markers of stem cell memory, unlike adult peripheral blood mononuclear cell–derived T cells. Moreover, placental-derived T cells are hypothesized to have a lower expression of effector or exhaustion markers, which could translate to a greater potential for proliferation in vivo.

“We believe the synergy between Celularity’s placental-derived cells and our OnCARlytic platform has the potential to shift the cellular medicine paradigm,” Leslie Chong, managing director and chief executive officer of Imugene, stated in a press release. “In preclinical studies, Celularity’s cellular therapies have shown the ability to overcome limitations that have hindered other approaches, including increased proliferation and persistence in vivo, resistance to T-cell exhaustion, and low immunogenicity, which allows for repeated dosing. These unique characteristics perfectly align with our vision for a combination treatment strategy, and we look forward to closely working together to bring this treatment strategy to the clinic and patients in need.”

The companies announced that nonclinical in vitro and in vivo combination studies are expected to commence in 2021.

References

1. Imugene and Celularity announce an exclusive strategic partnership to develop a novel oncolytic virus – allogeneic CAR T-cell immunotherapy combination for the treatment of solid tumors. News release. Imugene Ltd. and Celularity, Inc. August 5, 2021. Accessed August 5, 2021.

2. Imugene licenses CD19 oncolytic virus from City of Hope to turn CAR T therapy against solid tumors. News release. Imugene Ltd. and City of Hope. May 18, 2021. Accessed August 4, 2021. https://bit.ly/3lKmjvl

3. Park AK, Fong Y, Kim S-I, et al. Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. Sci Transl Med. 2020;12(559):eaaz1863. doi:10.1126/scitranslmed.aaz1863

4. Celularity and GX Acquisition Corp. announce merger agreement to create a publicly listed leader in allogeneic cellular therapy. News release. Celularity Inc. January 8, 2021. Accessed August 4, 2021. https://bit.ly/3yrrq6T