A global multidimensional analysis of the chimeric antigen receptor T-cell therapy clinical trial landscape and development trends

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has advanced significantly in oncology. To reveal the main trends affecting this field, we collected trial information of 1,908 CAR-T clinical trials using the INFORMA database. Since 2010, the number of CAR-T trials has increased sharply. China (1,006 trials) and the United States (549 trials) accounted for over 80% of all studies. Only 4.2% were sex-restricted studies and only 22% involved children. Although most studies were early phase, the number of phase III/IV trials has been steadily increasing. Research has predominantly focused on hematologic malignancies, including non-Hodgkin lymphoma, acute lymphoblastic leukemia, and multiple myeloma. While progress in solid tumors has been comparatively slower, it is steadily advancing. In addition, CAR-T therapy has demonstrated potential in treating certain autoimmune diseases. While CD19 molecule and TNF receptor superfamily member 17 remain dominant targets, other targets-including mesothelin and claudin 18 for solid tumors-were increasingly investigated. Several approved CAR-T products, such as Axicabtagene ciloleucel and Tisagenlecleucel, have undergone numerous clinical trials, resulting in expanded indications and refined treatment strategies. These findings offer some valuable insights into the status and prospects of CAR-T clinical trials.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40364-026-00910-6.

To the Editor,

Cancer remains a leading cause of death worldwide, with new cases projected to reach 35 million by 2050 [1]. Chimeric antigen receptor T-cell (CAR-T) therapy, which engineers a patient’s T cells to recognize and kill tumors, has shown remarkable success [2]. Compared with conventional treatments, CAR-T therapy offers greater tumor specificity and the potential for durable responses. To better understand global research trends, we analyzed CAR-T clinical trials from the INFORMA database [3].

On August 5, 2025, clinical research registration data were retrieved from the INFORMA (https://pharma.id.informa.com/) database. After manual deduplication, 1,908 CAR-T trials were identified worldwide, and China (1,006 trials) and the United States (549 trials) together accounted for over 80% of all trials (Fig. 1A-B). Globally, 39% of trials are ongoing, 19% planned, and 24% completed, indicating sustained research activity, whereas 12% were terminated and 6% closed, reflecting challenges related to efficacy, safety, and trial conduct (Fig. 1C, Table S1). Notably, only 11% of trials involve international collaboration; the limited scope likely results from regulatory and logistical hurdles. Regarding sex, 95.8% of trials did not stratify participants by sex, while only 4.2% were sex-restricted (1.7% male-only, 2.5% female-only) (Fig. 1D, Table S2). Among these sex-restricted studies, prostate cancer accounted for 78% of the male-only trials, whereas gynecologic cancers accounted for 68% of the female-only trials. However, the low proportion of sex-restricted trials suggests that sex-related factors may be overlooked (Fig. 1E, Table S3). Notably, accumulating evidence demonstrates sex-related differences in immunotherapy, including both therapeutic efficacy and adverse events [4]. For age, 98% of trials enrolled adults, 83% included older adults, and only 22% involved children though the study was not solely centered on pediatric patients (Fig. 1F, Table S4). Sponsorship is concentrated in China and the United States, with several funders from these two countries have funded more than 20 clinical trials (Fig. 1G-I, Table S5). In China, local biopharmaceutical companies dominate, while in the United States, both academic centers and pharmaceutical firms lead, reflecting a more diversified structure.

Fig. 1.

Global characteristics of CAR-T therapy clinical trials. (A) Worldwide distribution of 1,908 CAR-T therapy clinical trials. (B) Top 20 countries ranked by the number of CAR-T therapy clinical trials conducted. (C-E) The pie chart displays the global CAR-T therapy clinical trials categorized by clinical trial status (C), number of participating countries (D), and research population gender (E). (F) The bar chart shows the percentage of CAR-T therapy clinical trials involving children, adults, and older adults. (G) The top 6 sponsor countries of global clinical trials on CAR-T therapy. (H) Ranking of Chinese sponsors that have funded more than 20 clinical trials. (I) Sponsors in the United States with more than 20 funded clinical trials

Since 2010, CAR-T trial registrations have steadily increased, with over 250 new registrations in 2024 (Fig. 2A, Table S6). In hematologic malignancies, CAR-T therapy has achieved substantial progress (Fig. 2B, Table S7), with studies focused on non-Hodgkin lymphoma, acute lymphoblastic leukemia, and multiple myeloma, all ranking among the top indications in both overall trial numbers and phase III/IV studies [5]. Solid tumor CAR-T trials are limited by the immunosuppressive tumor microenvironment (TME) and a lack of safe, specific targets [6]. Tumor antigen variability further complicates treatment efficacy [7]. Despite these challenges, progress continues. CAR-T therapy has shown early efficacy in claudin 18 (CLDN18). 2-positive cancers [8], and combination strategies, such as with immune checkpoint inhibitors, are promising [9]. Approaches combining immunomodulators with key targets, such as mesothelin (MSLN) and CLDN18, may help overcome TME and antigen heterogeneity [10]. Beyond oncology, CAR-T therapy has also shown potential in treating autoimmune diseases like systemic lupus erythematosus [11]. Regarding targets, CD19 and TNF receptor superfamily member 17 (TNFRSF17) remain the primary focus of research (Fig. 2C, Table S8), while others-such as CD22, CD20, G protein-coupled receptor class C group 5 member D (GPRC5D), MSLN, and CLDN18-are also under active investigation. Products like Axicabtagene ciloleucel and Tisagenlecleucel have received regulatory approval, with more trials to expand indications and optimize regimens (Fig. 2D, Table S9). Also, multiple biomarkers-such as CD4, CD8A, C-reactive protein (CRP), and albumin-have been utilized in clinical trials to guide patient selection, assess efficacy, and monitor safety (Fig. 2E, Table S10). Analysis of phase III/IV trials shows that although their overall number remains limited, they are increasing (Fig. 2F), with continued focus on hematologic malignancies (Fig. 2G, Table S11) and potential expansion into solid tumors. The current low proportion of late-phase trials suggests that while CAR-T therapy has advanced significantly, it remains in the early stages of clinical development [12]. The United States and China lead in this area (Fig. 2H, Table S12), with the United States conducting more III/IV trials, reflecting its robust capabilities in drug development and translational research. Nevertheless, phase III/IV studies remain focused on a limited set of established products (Fig. 2I, Table S13) and conventional targets (Fig. 2J, Table S14), indicating substantial opportunities for exploring new targets and indications.

Fig. 2.

Distribution patterns of CAR-T therapy clinical trials. (A) The bar chart provides a comprehensive analysis of global CAR-T therapy clinical trials, integrating data on trial year, clinical phases, and the number of studies from 2010 to 2025. The inset in the figure compares the proportions of different clinical trial phases in CAR-T therapy studies. (B) The bar chart presents the top 20 diseases investigated in global CAR-T therapy clinical trials. (C) Top 20 drug targets investigated in global CAR-T therapy clinical trials. (D) Top 20 drugs studied in global CAR-T therapy clinical trials. (E) Utilization patterns of biomarkers across CAR-T therapy clinical trial record fields. (F) The bar chart presents the evolving trends and relative proportions of Phase III and IV CAR-T therapy clinical trials conducted between 2010 and 2025. (G-J) The lollipop charts illustrate the top 5 diseases (G), countries (H), drugs (I), drug targets (J) identified in Phase III and IV CAR-T therapy clinical trials

In summary, CAR-T therapy is advancing rapidly, with the United States and China leading. Future efforts should prioritize solid tumor applications, combination therapies, international collaboration, and inclusion of diverse populations to fully realize the potential of this transformative treatment.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

CAR-T

Chimeric antigen receptor T-cell

MSLN

Mesothelin

CLDN18

Claudin 18

TME

Tumor microenvironment

TNFRSF17

TNF receptor superfamily member 17

GPRC5D

G protein-coupled receptor class C group 5 member D

CRP

C-reactive protein

Author contributions

The study was conceived by CL, KX and WH. CL, ZW and JH wrote the main manuscript text. KH, JL, WZ and CL prepared the figures. All authors reviewed and edited the manuscript.

Funding

This study was supported by the Guangdong S&T Program (2023B1111030006), National Key Research and Development Program of China (2025YFC2424200), National Natural Science Foundation of China (82560599 and 82372766), China Postdoctoral Science Foundation (2025M782383), Guangdong Province Medical Science and Technology Research Fund (A2022541), Guangzhou Key Laboratory of Organ Transplantation (2025A03J4036), The Yixian Postdoctoral Launch Program Project (SYX-202507), Guangzhou Science and Technology Program (2025B03J0108), Yixian Clinical Research Project 5010 (SYS-5010-202503), Shenzhen Key Industry Research and Development Program (ZDCY20250901102503004), Guangdong Provincial Clinical Research Center for Urological Diseases (2020B1111170006), Science and Technology Planning Project of Guangdong Province (2023B1212060013).

Data availability

Original data generated and analyzed during this study are available in the INFORMA Pharma Intelligence database (https://pharma.id.informa.com/), a publicly accessible repository specializing in global clinical trial intelligence.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.