CAR-T therapy (chimeric antigen receptor t-cell immunotherapy) has been a favorite of the innovative drug market in recent years. However, up to now, the CAR-T therapies approved for marketing in the world are autologous products, which means after extracting cells from patients, T cells are activated by using gene engineering technology, with chimeric antigen receptors (CAR) targeting cancer antigens expressed on their surfaces, and then the proliferated cells are infused back into the patient's body. Subsequently, CAR-T cells use CAR as a targeting mechanism to specifically recognize tumor cells in the body and release a large number of effector molecules through immune action to kill the tumor cells.
Despite the impressive therapeutic effects of this type of therapy, its high pricing, restricted by the uniqueness of its manufacturing process, with marketed products priced over USD 1 million, significantly limits patient access. Furthermore, autologous CAR-T products involve steps such as gene modification, activation, culture, expansion, and modification, resulting in a relatively long preparation period (typically 2-3 weeks). Due to these limitations, universal CAR-T (UCAR-T), also known as off-the-shelf CAR-T or allogeneic CAR-T, has emerged and gained significant industry attention.
Since November, several transactions have occurred in the UCAR-T field among MNCs (multinational pharmaceutical companies). Notably, Roche acquired Poseida Therapeutics, a biopharmaceutical company focused on developing the UCAR-T therapy, on November 26 for a total value of USD 1.5 billion.
What are the advantages and limitations of UCAR-T? What is the current status of its development?
The Cost-Effective UCAR-T Attracts MNCs to Compete
Unlike autologousCAR-T therapy, UCAR-T is a type of CAR-T therapy prepared from allogeneic T cells collected from healthy donors. These T cells are genetically engineered and expanded on a large scale in vitro to produce off-the-shelf cell drugs. Since they are derived from healthy donors, they are not affected by the number and quality of the patient's T cells, resulting in a high preparation success rate. A single batch can meet the needs of hundreds of patients, offering absolute advantages in time and price.
Currently, UCAR-T cell therapy has sparked a R&D boom. Recently, Roche announced that it will acquire Poseida, a clinical-stage biopharmaceutical company, for a total value of approximately USD 1.5 billion. Poseida leverages a proprietary gene engineering platform technology to gradually transition from autologous to allogeneic CAR-T therapy.
In fact, Roche's collaboration with Poseida began in August 2022, with a focus on developing the UCAR-T therapy for hematologic tumors. The collaboration covers the R&D of multiple UCAR-T therapies targeting multiple myeloma, B-cell lymphoma, and other hematological indications.
With this significant acquisition of Poseida, Roche has gained access to Poseida's proprietary platform, the non-viral piggyBac DNA delivery system. This platform uses gene editing technology to deliver CAR molecules to T cells, with the advantage of generating CAR-T products with highly active stem cell memory T cells (TSCM cells). These cells exhibit more durable high-activity responses and lower toxicity. Additionally, non-viral vectors have low manufacturing costs, short production times, and low risks of mutagenesis and tumorigenesis.
Poseida's products under development also aim to address the limitations of CAR-T therapy, including issues such as duration of response and safety. Taking P-MUC1C-ALLO1, the pipeline under development, as an example, it is designed to be fully allogeneic, utilizing gene editing to eliminate or reduce reactions between the host and the graft, holding potential for the treatment of multiple solid tumors. In preclinical models, P-...
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