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Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment landscape for patients with hematological malignancies. However, its widespread application remains constrained by labor-intensive manufacturing processes, limited production capacity, and inconsistent clinical efficacy. In vivo CAR-T cell engineering, which generates CAR-T cells directly within the patient's body, eliminates the need for ex vivo cell processing and complex logistics while enhancing clinical outcomes, thereby addressing these challenges.
The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discovery and definition of regulatory T cells (Treg cells), revealing their importance in controlling autoreactive responses and pioneering the new field of Treg cell-mediated peripheral immune tolerance.
CAR-T cell therapy has shown significant efficacy in treating hematologic malignancies such as leukemia and lymphoma, prompting research into its application in various solid tumors. Among these tumors, glioblastoma (GBM) stands out as a particularly challenging target due to its aggressive nature and the lack of effective treatment options.
In recent years, CAR-T cell therapy has achieved remarkable success in treating blood cancers. However, it suffers from a critical weakness: the weeks-long and expensive preparation process, leaving many patients waiting for treatment and missing the optimal treatment window. Even more frustrating is that even when using a patient's own immune cells, these "modified warriors" can sometimes be accidentally attacked by other immune cells in the body, leading to the failure of the treatment.
The application of CAR-T cell therapy in solid tumors is limited by the suppressive tumor microenvironment (TME), which hinders T cell migration to tumor sites, leads to T cell exhaustion, insufficient T cell persistence, and limited endogenous anti-tumor immune responses. To address these therapeutic challenges, researchers have investigated combination strategies with immune checkpoint inhibitors (such as αPD-1, αCTLA-4, and αPD-L1) and immunomodulatory factors (such as IL-2, IL-7, IL-12, IL-15, and αTGFβ).
In a new study, a team of scientists from Peking University in China has developed a cancer therapy that has the potential to make lifesaving treatments accessible to patients everywhere. This new cancer therapy could expand access to advanced treatments. The study was published in the journal Cell.
To overcome these challenges, researchers have continuously upgraded and modified CAR-T cells. For example, incorporating different costimulatory signaling domains, such as CD28 or 4-1BB, addresses the short in vivo survival and poor activity of CARs. Simultaneously incorporating two costimulatory molecules into third-generation CARs enhances cytokine secretion. To better target the tumor microenvironment, researchers have developed fourth-generation CAR-T cells—"armored" T cells.
Have you ever wondered why some people seem naturally immune to certain bacterial infections? Or why do some recover quickly even after exposure to viruses? The answer may be a mysterious group of immune cells in our bodies called B-1a cells. For a long time, scientists have even debated whether humans actually possess these cells.
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy, accounting for approximately 15% of childhood acute lymphoblastic leukemia (ALL) and 25% of adult ALL. While cure rates for pediatric patients can reach 80%, the long-term survival rate for adult patients remains below 40%. More concerningly, more than half of patients relapse after treatment or fail to respond to standard therapy, with the median overall survival for relapsed/refractory T-ALL being only approximately eight months. Current treatment options primarily rely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT). However, these treatments are associated with significant toxicity and high failure rates, necessitating an urgent need for safer and more effective targeted therapy strategies.
Have you ever wondered why certain cancers caused by the human papillomavirus (HPV) are so stubborn, even defying advanced immunotherapies? HPV-related cancers kill over 300,000 people worldwide each year, with cervical and head and neck cancers being particularly common. While HPV vaccines have been highly successful in preventing these diseases, treatment options for established HPV-positive tumors remain limited. In recent years, scientists have gradually realized that immune defection within the tumor microenvironment (TME) may be the key.
