New Collaboration to Develop ROR1 Targeted Cell Therapies

Oncternal and Celularity hope to produce ROR1-targeted NK, CAR-NK, and CAR T-cell therapies.

Oncternal Therapeutics and Celularity are collaborating to develop placental derived-cellular therapies targeting receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1).1

The research collaboration between the companies will combine cirmtuzumab, Oncternal’s monoclonal antibody targeting ROR1, with the natural killer (NK) cells Celularity is developing. The companies hope to develop ROR1 targeted chimeric antigen receptor (CAR) cells with both Celularity’s CYNK and CyCART cell therapy platforms and plan to investigate these possibilities in preclinical studies.

“Our research studying ROR1 suggests the potential for a range of new targeted therapeutics, capable of addressing a wide variety of both solid tumors and hematological malignancies,” said James Breitmeyer, MD, PhD, founder, president and chief executive officer, Oncternal, in a statement.1 “We believe that targeted cellular therapies have the potential to extend the clinical benefit of our research and improve the standard of care for patients. However, the current limitations in efficacy, safety and availability of cellular therapies hinders their broader use. Celularity’s approach, leveraging the ability of placental-derived cells to differentiate and expand, has the potential to overcome these obstacles and could potentially offer more potent, tolerable and accessible cellular medicines and, in combination with our ROR1 targeting antibodies, address the significant unmet needs of patients.”

ROR1 has potential as a target in both solid tumors and hematological malignancies, in which it is highly expressed. Adding to the importance of the target, cancer cells with ROR1 have an aggressive phenotype and survival advantage.

READ MORE: Celularity Expands Natural Killer Cell Therapy Trial to Relapsed/Refractory AML Following Patient Conversion

Cirmtuzumab decreases tumor cell proliferation and survival by blocking Wnt51-induced activation. It bonds to ROR1 on leukemia and lymphoma cells but not adult tissues. Cirmtuzumab will be evaluated in combination with Celularity’s CYNK-101, which is a genetically modified NK cell therapy. In addition to the CYNK platform, Celularity also has CAR-NK and CAR T-cell programs, which they will investigate with ROR1 targeting.

“We are thrilled to enter this partnership with Oncternal to forge new therapeutic strategies for both solid tumors and hematological malignancies using our allogeneic placental-derived cell therapy product candidates with their innate stemness,” Robert J. Hariri, MD, PhD, founder, chairperson and chief executive officer, Celularity, added to the statement.1 “Oncternal’s work has established ROR1 as an exciting target that could be utilized for the development of new and novel cellular medicines, and there is an immense potential for synergy combining two novel approaches to create exciting new pipeline candidates targeting a wide range of cancers. We look forward to working closely together to lead the next evolution of cellular medicines.”

Celularity also recently entered into a collaboration with Imugene focused on assessing the therapeutic potential of a combination approach to treating solid tumors using CAR T-cell therapy and an oncolytic virus.2 The company announced their plans to launch nonclinical in vitro and in vivo studies this year to assess the novel combination of Celularity’s CD19-targeting, placental-derived, off-the-shelf allogeneic CAR T cell therapy, CyCART-19, with Imugene’s CF33-CD19, a CD19 oncolytic virus technology.

“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,” Hariri said in a statement at that time.2 “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.”

1. Oncternal Therapeutics and Celularity Enter into Research Collaboration to Evaluate Targeted Placental-Derived Cellular Therapies. News release. Oncternal Therapeutics. September 20, 2021.
2. 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. Celularity. August 5, 2021.
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