Key Timeline of CAR-T Therapy: The Evolu

Key Timeline of CAR-T Therapy: The Evolutionary Journey from Clinical Trial Breakthroughs to Global Approval

 

1. Concept Foundation and Early Exploration (1991-2010)

 

1991: The concept of CAR-T cells was officially established. Three laboratories, led by Irving and Weiss, Letourneur and Klausner, independently developed the first-generation CAR-T cells. These cells combined the single-chain variable fragment of monoclonal antibodies with the CD3ζ intracellular signaling domain, enabling MHC-independent target cell lysis.

2010: Adult patient Bill Ludwig became the first adult to receive CAR-T therapy at the University of Pennsylvania. His refractory chronic lymphocytic leukemia (CLL) achieved complete remission after treatment, marking the first critical clinical validation of CAR-T therapy's efficacy in adult patients.

 

2. Pediatric Clinical Breakthroughs and Technological Maturation (2012-2016)

 

April 2012: Six-year-old Emily Whitehead, the world's first pediatric patient to receive CD19-targeted CAR-T therapy, survived severe cytokine release syndrome (CRS) with successful treatment using tocilizumab and achieved long-term cancer-free survival. This validated CAR-T therapy's efficacy in pediatric acute lymphoblastic leukemia (ALL) and laid the groundwork for subsequent clinical trials.

2012-2016: Large-scale clinical trials of second-generation CAR-T cells (equipped with CD28 or CD137 co-stimulatory domains) targeting CD19 were conducted. These cells demonstrated an overall response rate of 44% to 91% and a complete response rate of 28% to 68% in relapsed/refractory B-cell malignancies, with complete response rates exceeding 80% in acute leukemia-related trials.

 

3. Global First Approvals and Rapid Expansion (2017-2021)

 

2017: The U.S. FDA approved Kymriah™, the world's first CAR-T therapy, for the treatment of pediatric and young adult B-cell ALL—83% of patients in clinical trials achieved complete remission. In the same year, the second CAR-T therapy, Yescarta™, was approved, officially ushering CAR-T therapy into the commercialization phase.

2020: The FDA approved Tecartus™, the third CAR-T therapy, expanding its indication to specific types of lymphoma.

2021: The FDA approved Breyanzi™, the fourth CAR-T therapy, and simultaneously granted approval to Abecma™, the first AbMA-targeted CAR-T therapy. Based on data from the KarMMa clinical trial, Abecma™ filled the gap in the treatment of multiple myeloma.

 

4. Regulatory Breakthroughs in China and Global Collaboration (2018-2024)

 

March 2018: China approved its first Investigational New Drug (IND) application for a CAR-T therapy (Ciltacabtagene Autoleucel), marking the official launch of China's CAR-T therapy clinical research and development process.

2022: Ciltacabtagene Autoleucel was first approved by the U.S. FDA, followed by approvals from the European Medicines Agency (EMA) in May and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) in September. It became the first China-U.S. co-developed CAR-T product recognized by multiple global regulatory authorities.

August 2024: Ciltacabtagene Autoleucel received conditional approval in China, completing its approval layout in major global pharmaceutical markets and improving the clinical accessibility of CAR-T therapy in China.

 

5. Technological Iteration and Indication Expansion (Ongoing)

 

As of 2025, 13 CD19- or BCMA-targeted CAR-T products have been globally approved for the treatment of various hematological malignancies. Clinical trials of fourth-generation CAR-T cells (TRUCKs) have made progress, showing long-term remission potential in multiple myeloma treatment, while fifth-generation CAR-T cells focus on optimizing safety and efficacy.

Research directions are expanding from hematological malignancies to solid tumors (e.g., prostate cancer, glioblastoma) and non-oncological diseases, opening up broader application prospects for CAR-T therapy.