Core Viewpoint - The article discusses the potential of engineered long-lived CAR-T cells as a delivery platform for biologics, particularly for chronic diseases requiring long-term treatment, highlighting the advantages of a single-dose, long-lasting therapeutic approach [2][3][15]. Group 1: Challenges of Current Biologics - Recombinant proteins, while effective in treating various diseases, have a short half-life in the body, necessitating repeated injections for chronic conditions [2]. - GLP-1 drugs, such as semaglutide and tirzepatide, require weekly injections to maintain their effects, leading to potential weight regain upon discontinuation [2]. - Repeated infusions of peptide/protein biologics can lead to the formation of immune responses, reducing efficacy and potentially causing immunopathological issues [2]. Group 2: Innovations in Delivery Platforms - The research team from Tsinghua University developed long-lived CAR-T cells as a novel delivery platform for biologics, achieving stable delivery of GLP-1 in animal models with a single infusion [3][14]. - Previous methods using AAV vectors for delivering therapeutic proteins have limitations due to their short duration of effect, typically less than two years [5]. - CAR-T cells have shown promise in treating rare diseases, functioning as "living" drugs that can replicate and survive in the body, potentially achieving long-term efficacy [5]. Group 3: Recent Research Developments - The team created immortal-like functional T cells (T IF cells) through gene editing, which can exist safely in the body for extended periods and provide long-term tumor relief [6]. - Further modifications to T IF cells allowed for the targeting and elimination of eosinophils, providing a potential long-term treatment for allergic asthma with a single injection [9]. - The GD2T IF cells were engineered to deliver GLP-1, effectively controlling weight and blood sugar levels in obese mice with a single infusion, achieving "cure" indicators [14][15]. Group 4: Practical Considerations for CAR-T Cell Therapy - For CAR-T cells to be a practical delivery platform for chronic disease biologics, three conditions must be met: elimination of chemotherapy preconditioning, long-term maintenance of sufficient CAR-T cell numbers, and careful selection of targets to avoid damage to normal cells [11][12][13]. - The GD2 target was chosen due to its overexpression in certain tumors and minimal expression in normal tissues, showing good efficacy in clinical trials without significant off-target effects [13]. Group 5: Future Implications - The research indicates that the engineered GD2T IF cells could serve as a reliable platform for stable production of biologics, offering a one-time treatment solution for chronic diseases [15]. - Although current CAR-T cell therapies are costly, the expectation is that as prices decrease, this method will become more cost-effective compared to repeated injections of biologics [15].