Huazhong University of Science and Technology Union Hospital Licenses CAR-T Efficacy Monitoring Technologies for RMB 2 Million

Recently, Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology released a public notice on the transformation of scientific and technological achievements, indicating that the hospital intends to“Universal CAR Copy Number Detection Reagent, Its Applications and Application Methods, and Method for Detecting CD19 Expression”Two patented technologies were transferred to Wuhan Suituokang Biotechnology Co., Ltd. through agreement-based pricing, with the proposed transfer amountRMB 2 million. The inventors of this patented technology are the team led by Professor Mei Heng from the Department of Hematology at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

The team tackled key monitoring challenges in CAR-T therapy by successfully developing a highly universal and precise CAR copy number detection technology, and establishing a dynamic monitoring system for CD19 expression and alternative splicing isoforms. This provides important tools for personalized assessment of CAR-T therapy and elucidation of relapse mechanisms, further advancing precision monitoring and efficacy optimization in the field of cell therapy.

The Assignee of the Patent Technology in QuestionWuhan Sitech Biotechnology Co., Ltd., is an innovative enterprise focused on the research, development, and translation of biotechnology. Rooted in the fields of life sciences and healthcare, the company is dedicated to the development and industrialization of cutting-edge detection technologies, diagnostic reagents, and therapeutic companion products.

This technology package is a molecular testing solution designed for comprehensive monitoring throughout the course of CAR-T cell therapy. One of the technologies enables precise monitoring of CD19 expression levels and alternative splicing isoforms in tumor cells following anti-CD19 CAR-T therapy, using specific primers. It can be used to evaluate treatment efficacy and mechanisms of relapse.

Another technology offers a universal, high-sensitivity assay for CAR copy number detection. By targeting conserved sequences in HIV-modified lentiviral vectors, it enables precise quantification of CAR gene copy numbers in diverse CAR-T products.

Together, they comprehensively enhance the efficacy monitoring system, spanning from in vivo expansion of CAR-T cells to the dynamic expression of tumor targets.

CAR-T cell therapy, fully known as chimeric antigen receptor T-cell immunotherapy, is a revolutionary cancer immunotherapy. It does not belong to traditional drugs or surgery, but rather is a"Live Biotherapeutic Products"。

Its core principle isBy using genetic engineering technology, the patient's own T cells are modified in vitro.Scientists equip T cells with a “navigation head” known as a “chimeric antigen receptor.” This CAR structure enables T cells to precisely recognize specific targets on the surface of tumor cells (such as the CD19 protein). After expansion, these “armed” and “enhanced” CAR-T cells are infused back into the patient’s body, where they act like special forces to selectively track and efficiently eliminate tumor cells.

B-cell malignancies are a broad category of cancers originating from B lymphocytes (immune cells responsible for antibody production) or their precursor cells. A common feature of these diseases is the uncontrolled malignant proliferation and accumulation of B cells at certain stages of development and differentiation. The main common types include:

1. Acute B-lymphoblastic leukemia (B-ALL):Originating from immature B-cell precursors in the bone marrow, it is common in both children and adults and progresses rapidly.

2. Non-Hodgkin Lymphoma (e.g., Diffuse Large B-Cell Lymphoma, etc.):Originating from relatively mature B cells in lymph nodes or lymphoid tissue, it is the most prevalent type of lymphoma.

3. Multiple Myeloma:Originating from plasma cells in the bone marrow (the terminal stage of B-cell development), it primarily affects the skeletal and hematopoietic systems.

The reason why the association between CAR-T therapy and B-cell malignancies is crucial is that>95%B-cell malignancies all specifically and highly express the CD19 molecule on their surface, making CD19 a nearly perfect ideal target.

Therefore, the earliest globally approved and most clinically mature CAR-T therapies are all CD19-targeted CAR-T products, which have demonstrated transformative efficacy in treating relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and certain types of lymphoma, thereby reshaping the treatment landscape for these diseases.

The monitoring of CAR-T cell quantity (copy number) and the expression quality of the tumor target CD19, addressed by this patent technology package, is precisely aimed at optimizing and ensuring the efficacy and safety of this cutting-edge therapy in patients with B-cell malignancies.

The core diseases jointly targeted by this patent technology portfolio are B-cell malignancies, primarily including acute B-lymphoblastic leukemia (B-ALL), lymphoma, and multiple myeloma. These diseases share the common characteristic of malignant transformation of B cells or their precursor cells, leading to abnormal proliferation in the blood, bone marrow, or lymphatic system.

Currently, the revolutionary clinical regimen for this type of hematologic malignancy isChimeric Antigen Receptor (CAR) T-Cell TherapyThis therapy employs genetic engineering techniques to introduce a chimeric antigen receptor (CAR) construct, capable of recognizing specific tumor surface antigens (such as CD19), into the patient’s own T cells, thereby engineering a “living drug” that can precisely identify and eliminate tumors.

Taking CD19-targeted CAR-T therapy as an example, it has achieved initial complete remission rates of approximately 70–90% in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), becoming a critical life-saving intervention. However, significant clinical limitations persist despite this remarkable efficacy. First, the effectiveness and safety of the treatment are highly dependent on the dynamic behavior of the infused CAR-T cells within the patient’s body, including their engraftment, peak expansion, and long-term persistence.

Clinical studies have demonstrated that the early expansion kinetics of CAR-T cells are associated with therapeutic response and adverse events such as cytokine release syndrome, whereas their long-term persistence correlates with the duration of remission. Therefore, precise quantitative monitoring of in vivo CAR-T cells is a core requirement for optimizing clinical patient management and predicting both therapeutic efficacy and safety risks.

However, existing monitoring methods have fundamental flaws. Currently, quantitative fluorescent PCR (qPCR) is the most commonly used technique in clinical and laboratory settings to detect CAR copy numbers, thereby indirectly reflecting the quantity of CAR-T cells. This technique requires establishing a standard curve using a series of standards with known concentrations, and then calculating the results based on the cycle threshold (Ct value) of the amplification for the test samples.

However, due to variations in CAR structures across different companies and products—particularly in the sequences of their single-chain variable fragments (scFv) and signaling domains (e.g., 4-1BB-CD3ζ)—primers and probes designed for a specific CAR construct are not universally applicable. For instance, there is a lack of publicly available and validated detection tools for relma-cel, an already marketed CAR-T therapy.

Furthermore, reliance on reference standards and the complexity of experimental procedures hinder the widespread and standardized clinical implementation of this technique, while also compromising the accuracy and reproducibility of quantitative results.

On the other hand, even if CAR-T cells successfully expand in vivo, there are stillUp to 30-60%Patients face the dilemma of post-treatment relapse, with “antigen-negative escape” being the primary challenge. This refers to tumor cells evading recognition and attack by CAR-T cells through downregulation or complete loss of the CD19 antigen.

Current research reveals,One of the most critical escape mechanisms is alternative splicing of CD19 gene mRNA.Alternative splicing is the process by which cells differentially splice precursor RNA to generate mature mRNA, thereby producing multiple isoforms. Under therapeutic pressure selection, tumor cells may preferentially express aberrantly spliced CD19 mRNA.

Protein isoforms translated from these aberrant mRNAs often lack the extracellular domain, transmembrane domain, or key antigenic epitopes specifically recognized by CAR-T cells, resulting in failure of CD19 protein to localize to the cell membrane or rendering it unbindable by CAR-T cells even if expressed.

To thoroughly validate this critical mechanism of relapse and guide clinical decision-making, it is essential to accurately and dynamically monitor the expression ratio of normal CD19 to various aberrantly spliced isoforms in patients’ tumor cells.

However, due to the unique and complex nature of these isoform sequences, it is extremely challenging to establish a stable, reliable detection system suitable for clinical samples. This technical bottleneck has severely hindered researchers’ in-depth exploration of recurrence mechanisms and has prevented clinicians from predicting in advance which patients may experience treatment failure due to antigen escape.

In summary, current clinical practice of CAR-T cell therapy for B-cell malignancies faces two major monitoring blind spots:

First, it is not possible to universally, accurately, and conveniently quantify the in vivo kinetics of CAR-T cells.

Second, it is unable to effectively monitor the integrity of CD19 tumor target expression, particularly making it difficult to identify antigen-negative escape caused by alternative splicing.

These two limitations collectively hinder accurate assessment of therapeutic efficacy, in-depth understanding of recurrence mechanisms, and individualized precision management of patients.

To this end, the patent technology package proposes an integrated solution aimed at overcoming the aforementioned core bottlenecks.

The core advantages and advanced nature of this patent technology package lie in itsProvides an integrated and precise molecular monitoring system,It fundamentally addresses two critical challenges in the efficacy assessment and relapse monitoring of current CAR-T cell therapy.

Its advancement does not stem from a breakthrough in a single technology, but rather from the organic synergy of two patented technologies,Achieved dual, simultaneous, and precise control over the dynamics of “cellular drugs” and the status of “tumor targets” throughout the entire treatment course.

First, in monitoring the in vivo kinetics of CAR-T cells,This technology package abandons the traditional design paradigm that relies on specific CAR structural sequences and innovatively adopts a universal strategy centered on “targeted delivery vectors” rather than the “cargo.” The majority of clinical CAR-T products introduce CAR genes into T cells using lentiviral vectors engineered from HIV. This modified viral genome (referred to as the provirus) stably integrates its conserved regions into the host cell genome.

This patent ingeniously targets the highly conserved 5’LTR region in prior viral sequences to design universal detection probes and primer pairs. This means that, regardless of changes in the targeting antibody (scFv) or signaling domain within the CAR structure, as long as it is delivered by such HIV-derived lentiviral vectors, it can be precisely captured and quantified by the same set of detection tools.

This approach effectively overcomes the limitation of existing detection methods, which require “product-specific reagent kits” due to the structural diversity of CARs, thereby enabling universal detection of various CAR-T products, including lisocabtagene maraleucel. Combined with digital PCR technology, this method allows for direct absolute quantification without the need for a standard curve, offering higher sensitivity, specificity, and reproducibility. It provides a reliable tool for large-scale, standardized clinical monitoring of CAR-T cell expansion and persistence.

Secondly, in assessing the risk of tumor immune escape,This technology package establishes, for the first time, a mature detection system capable of precisely quantifying key alternatively spliced isoforms of the CD19 gene. Antigen-negative relapse, particularly immune escape caused by aberrant splicing of the CD19 gene, is a major cause of CAR-T therapy failure.

By conducting an in-depth analysis of the transcript structure of the CD19 gene, this patent meticulously designs a detection panel comprising five pairs of primers targeting the full-length transcript as well as two important deletion splice isoforms (Δex2 and Δex5-6). These primers specifically target exon junctions or shared regions unique to different splice isoforms, functioning like highly specific “molecular keys” that can accurately distinguish and quantify the proportions of various CD19 mRNA variants from complex RNA samples.

Meanwhile, the use of a reference gene (HPRT1) with matched expression abundance ensures the accuracy of relative quantification results even when CD19 expression levels are low. This method enables clinicians and researchers to dynamically monitor changes in the ratio of functional CD19 to defective CD19 isoforms in tumor cells before and after treatment, thereby providing early warning of antigen-modification escape and offering crucial molecular evidence for elucidating relapse mechanisms and guiding subsequent therapeutic strategies.

In summary, the advancement of this patent technology package is reflected in its forward-looking and systematic design. It does not merely provide two isolated detection methods, but ratherWe have established a comprehensive, closed-loop monitoring framework spanning from “effector cells” (via universal CAR copy number monitoring) to “target integrity” (through precise splice isoform analysis).By combining generality with specificity, and quantitative analysis with qualitative assessment.

This technology package significantly enhances the precision and depth of efficacy assessment for CAR-T therapy, strongly propelling tumor immunotherapy toward truly personalized and precise management.

The current CAR-T cell therapy market is facing two core challenges: traditional autologous CAR-T therapies encounter industrialization bottlenecks such as long manufacturing lead times, high costs, and significant batch-to-batch variability; meanwhile, the dynamic changes of CAR-T cells in vivo during treatment and the risk of tumor antigen escape pose clinical management difficulties for efficacy assessment and recurrence monitoring. To overcome these limitations, biotechnology companies both domestically and internationally are actively advancing next-generation technologies.

GileadAcquisition in 2025 Interius, advancing the joint development of itsINT2104(Lentiviral vector, targeting CD19, for B-cell malignancies) The pipeline completed its first patient dosing in Australia in 2024. It is the world’s first in vivo CAR-T therapy to enter human clinical trials and is currently in Phase I, with plans to submit a Biologics License Application (BLA) in 2026.

AbbVieAcquisitions in 2025Capstanafterwards, obtain itsCPTX-2309(LNP delivery, targeting CD19, for B cell-mediated autoimmune diseases), this pipeline is in Phase 1, and related research has been published in Science.

UmojaDevelopedUB-VV111(Nanobody lentiviral vector targeting CD19 for hematologic malignancies) Received FDA IND approval to enter Phase I in 2024, concurrently withReindeer BiopharmaCo-developmentUB-VV400(Targeting CD22 for hepatocellular carcinoma), also in Phase I.

Keji Biologicsis a leading CAR-T company in China, with approved products on the marketBCMA CAR-T Products and the Highly Anticipated Solid Tumor Claudin18.2 CAR-T Cells, having long been established in the field of universal CAR-T, has developed the THANK-uCAR technology platform and its upgraded version, the THANK-u Plus platform. The latter can overcome the potential impact of NK cells on the efficacy of universal CAR-T cells, enabling sustained expansion in the presence of NK cells with varying NKG2A expression levels, with significantly superior expansion compared to the former. It also demonstrated superior anti-tumor efficacy in animal studies. Based on the THANK-u Plus platform, universal BCMA CAR-T, CD19/CD20 CAR-T, and CD38 CAR-T products have been developed, and multiple investigator-initiated trials (IITs) have been launched.

Bioray LaboratoriesAllogeneic Universal CAR-T Shows Outstanding Performance in Autoimmune Diseases: On October 4, 2024, Nature featured a headline article on the clinical study of allogeneic universal CAR-T therapy for autoimmune diseases, conducted collaboratively by Professor Xu Huji’s team at Shanghai Changzheng Hospital and Professors Liu Mingyao and Du Bing’s teams at East China Normal University. The study successfully treated three patients with scleroderma using BRL-303, an allogeneic universal CAR-T cell product developed by Biocytogen.

In January 2025, BonBio, in collaboration with the aforementioned research teams and clinical teams from Shanghai Changzheng Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, and others, jointly conductedResearch on the Treatment of Autoimmune Diseases with Next-Generation Allogeneic Universal CAR-T Therapy, was selected by the journal Cell for its 2014–2024 Major Milestones list as a Research Article, and this research was officially published in Cell on July 15, 2024.This represents the first international report of successful treatment of autoimmune diseases with allogeneic universal CAR-T cells, and also marks the first time that the top-tier academic journal Cell has published research on CAR-T cell therapy for autoimmune diseases.

In summary, this patent technology portfolio precisely addresses the unmet needs in the precision management of cell therapy. Its development prospects are closely tied to the evolution of the entire CAR-T industry toward greater efficiency, accessibility, and controllability. Subsequent industrialization strategies and the accumulation of clinical data will determine whether its theoretical advantages can be translated into actual market presence and application status.