VectorBuilder's partner, Ucello, announced that its CD19-targeting umbilical cord blood-derived allogeneic CAR-T cell therapy, UC101, received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) on January 11, 2025.  VectorBuilder has provided highly customized end-to-end CDMO solutions to support this clinical pipeline.

Dr. Bruce Lahn, Chief Scientist at VectorBuilder, commented, "Congratulations to Chengdu Ucello on the FDA IND approval of UC101. As the world’s first umbilical cord blood-derived allogeneic CAR-T product, UC101 represents groundbreaking innovation, offering new hope for treating various diseases. We are honored to support this milestone and look forward to deepening our collaboration to advance clinical pipelines, bringing safer and more effective therapies to patients worldwide."  

World's First FDA IND-Approved Umbilical Cord Blood-Derived Allogeneic CAR-T Product 

UC101 is the world’s first FDA IND-approved umbilical cord blood-derived allogeneic CAR-T therapy. T cells derived from umbilical cord blood possess the natural advantages of low immunogenicity and being in an early differentiation state. These advantages alleviate the risk of host-versus-graft response (HvGR), leading to more efficient in vivo proliferation, ultimately improving the persistence of the allogeneic CAR-T cells and significantly enhancing the expected therapeutic outcomes. Furthermore, approximately 90 percent of the umbilical cord blood-derived T cells are naïve T cells; multipotent precursors of various types of mature T cells. Following cell expansion, the product retains roughly 80 percent stem cell-like memory T cells (Tscm) and central memory T cells (Tcm). These play a crucial role in generating an improved CAR-T drug profile with greater proliferation and persistence. 

Technical Innovation and Cost Efficiency  

UC101 is the first CAR-T product to utilize a stable producer cell line for lentiviral vector manufacturing. This production strategy does not require plasmid DNA as critical starting material for virus packaging. Without the need to manufacture clinical-grade plasmid DNA, this strategy greatly reduces the cost of manufacturing. On top of the optimized overall manufacturing cost, this approach easily achieves higher consistency between batches, steady quality attributes, and, most importantly, strong potency of the lentiviral vector.  

Incorporating an advanced design for gene editing, UC101 minimizes immunogenicity and demonstrates optimal efficacy while keeping adverse events under tighter control. Large-scale, GMP-compliant production using umbilical cord blood enables a batch size sufficient for treating over 100 patients, making CAR-T therapy more accessible to patients in need. 

10-Fold Leap in Viral Titer and Decreased Patient Cost with VectorBuilder's Tailored CDMO Services

VectorBuilder provides end-to-end CDMO services, including producer cell banking, lentiviral process and analytical development, multi-batch GMP manufacturing, and quality control. Through dedicated process development by the VectorBuilder CDMO team, the current upstream process is able to achieve 5E+8 TU/mL of lentiviral vector in the harvest, being at least 10-fold higher than that of transient transfection approach under similar scale and condition. The downstream purification strategy has also been developed specifically for this lentiviral vector by VectorBuilder to achieve a physical particle recovery rate of more than 30 percent, with the highest functional particle recovery reaching 50 percent. Under the EU QP-certified GMP system, VectorBuilder has developed a consistent lentiviral vector manufacturing process which can help bring down the cost per single dose of CAR-T cell therapy to around 1,400 USD. 

The FDA IND approval of UC101 further showcases VectorBuilder’s mature platform of lentiviral manufacturing. In addition to its extensive FDA IND experience with transfection-based lentiviral vector processes, VectorBuilder has established a robust system to adopt advanced technologies, enabling the development, testing, and manufacturing of innovative CMC for cell and gene therapy pipelines.