MUC1 Chimeric Antigen Receptor (CAR): A Comprehensive Guide and Our Service & Product Introduction

MUC1 is overexpressed in a variety of solid tumors, and MUC1 CAR-T cell therapy, as a novel immunotherapy, has broad application prospects in the treatment of MUC1-positive tumors. With the continuous optimization of CAR structure, the improvement of targeting specificity, and the breakthrough of combination therapy strategies, MUC1 CAR-T cell therapy is expected to become an important treatment option for advanced MUC1-positive tumors, bringing new hope to patients.

RGBiotech’s MUC1 CAR expression plasmid vectors and customization services will provide strong support for the research and development of MUC1-targeted immunotherapy, accelerating the transformation of scientific research achievements into clinical applications. If you are interested in our MUC1 CAR expression plasmid vector products or customized services, or have any questions about MUC1 CAR research and development, please feel free to contact us. We will provide you with professional technical consultation and high-quality services to help you advance your MUC1-targeted immunotherapy research and development project.

Our MUC1 CAR Expression Plasmid Vector Products and Custom Services

MUC1 (Mucin 1, Cell Surface Associated), also known as CD227, is a key transmembrane glycoprotein that plays critical roles in physiological and pathological processes, especially in tumorigenesis. As a promising target for immunotherapy, MUC1 has attracted extensive attention in the development of Chimeric Antigen Receptor (CAR) technology. RGBiotech is dedicated to providing high-quality MUC1 CAR expression plasmid vectors and customized vector construction services, supporting global researchers and biopharmaceutical enterprises in advancing MUC1-targeted immunotherapy research and development.

RGBiotech has long been engaged in the research and development, production, and customization of gene engineering products, and has rich experience in the field of CAR plasmid vectors. We provide a full range of MUC1 CAR expression plasmid vector products, covering different generations of MUC1 CAR, and can also provide personalized plasmid vector construction customization services according to the specific needs of customers, to fully support the research and development of MUC1 CAR-related projects. Please contact us at admin@rgbiotech.com for more information.

Product Features

Product Applications

Customized Plasmid Vector Construction Services

In addition to standard MUC1 CAR expression plasmid vectors, we also provide personalized plasmid vector construction customization services to meet the specific needs of customers.
1) Custom CAR Structure Design: According to the customer's research needs, design and construct MUC1 CAR plasmid vectors with specific structures.
2) Vector Backbone Customization: Customize vector backbones according to the customer's delivery method (such as non-viral, lentiviral, retroviral, AAV) and application scenario, and optimize the vector structure to improve expression efficiency and stability.
3) Label and Selection Marker Customization: Customize fluorescent labels (such as special fluorescent proteins) and antibiotic selection markers according to the customer's experimental needs.
4) Codon Optimization: Optimize the codon of the MUC1 CAR gene according to the codon preference of the target cell to improve the expression efficiency of the CAR gene.
5) Full-Service Support: Provide one-stop services from vector design, construction, sequencing, quality inspection to delivery, and provide professional technical consultation and after-sales service to solve the problems encountered by customers in the experimental process.

Why Choose Our MUC1 CAR Plasmid Vectors and Custom Services?

In the field of MUC1 CAR research and development, choosing high-quality plasmid vectors and professional customization services is crucial to the success of the project. RGBiotech has the following advantages to meet your needs.
1) Professional R&D Team: We have a professional R&D team with rich experience in CAR vector design and construction, who can provide personalized solutions according to customer needs.
2) Strict Quality Control: We adhere to international quality standards, and each batch of products undergoes strict quality inspection to ensure product quality and reliability.
3) Comprehensive Product Line: We provide a full range of MUC1 CAR plasmid vectors covering different generations and vector backbones, meeting the diverse needs of customers. 4) Efficient Customization Service: We have a mature customization service process, which can complete vector design, construction, and delivery in a short time, improving the efficiency of customer research and development.
5) Professional Technical Support: We provide one-stop technical consultation and after-sales service, solving the problems encountered by customers in the experimental process and ensuring the smooth progress of the project.

Introduction of MUC1

The human MUC1 gene (Gene ID: 4582, HGNC: 7508, Ensembl: ENSG00000185499.17) is located on chromosome 1q22 (hg38 chr1: 155,186,123 - 155,192,867), with a total length of approximately 6,745 bp and 5 coding exons. It encodes a membrane-bound protein belonging to the mucin family, and alternative splicing results in multiple transcript variants. A notable feature of the MUC1 gene is its highly polymorphic Variable Number Tandem Repeats (VNTR) domain, which contributes to the diversity of MUC1 protein isoforms. The Gencode transcript of MUC1 is ENST00000342482.8, and its coding region spans 6,709 bp, encoding a 166-amino-acid precursor protein.

MUC1 is a heterodimeric glycoprotein composed of two non-covalently bound subunits: the N-terminal alpha subunit (MUC1-N, also known as MUC1-nt) and the C-terminal beta subunit (MUC1-C, also known as MUC1-ct). The protein undergoes proteolytic cleavage to form this heterodimeric complex, which is essential for its biological functions.
1) MUC1-N (Extracellular Domain): Located outside the cell membrane, it contains a variable number of 20-amino-acid tandem repeats (VNTR) and is highly O-glycosylated. This highly glycosylated region extends outward from the cell surface, forming a physical barrier on mucosal surfaces.
2) MUC1-C (Transmembrane and Intracellular Domain): Consists of an extracellular segment, a transmembrane segment, and a cytoplasmic tail. The cytoplasmic tail is the key part of signal transduction, which can be phosphorylated and interact with other proteins to regulate downstream signaling pathways. Under the mediation of the SEA domain, MUC1 can undergo autoproteolytic cleavage; when receiving inflammatory signals (such as IFN-γ and TNF-α), MUC1-N is released, thereby activating MUC1-C and initiating downstream signaling pathways.

Under physiological conditions, MUC1 plays dual roles in maintaining tissue homeostasis and immune regulation.
1) Barrier Protection: The highly glycosylated MUC1-N forms a protective layer on the surface of epithelial cells, preventing bacterial invasion and enzyme damage, and maintaining the integrity of the epithelial barrier.
2) Cell Adhesion and Anti-Adhesion: MUC1 can act both as an adhesion and an anti-adhesion protein, regulating cell-cell and cell-matrix interactions to maintain normal tissue structure.
3) Intracellular Signaling Regulation: The MUC1-C cytoplasmic tail participates in the regulation of multiple signaling pathways (such as ERK, Src, NF-κB, and PI3K/Akt), involving cell proliferation, differentiation, apoptosis, and DNA damage response. It also regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response.
4) Immune Regulation: In the context of infection or inflammation, MUC1 can bind to viruses through sialic acid structures at the end of sugar chains (such as limiting influenza A infection) and regulate the intensity of inflammation to prevent immune damage.

MUC1 is mainly expressed on the apical surface of epithelial cells lining the mucosal surfaces of various tissues, showing strict polar expression under normal physiological conditions. The main expression tissues include: 1) Respiratory system: Lung epithelial cells; 2) Digestive system: Stomach, pancreas, and intestinal epithelial cells; 3) Reproductive system: Breast epithelial cells, uterine cervical epithelial cells; 4) Other tissues: Salivary gland epithelial cells, kidney epithelial cells, and exosomes in various extracellular compartments. In normal tissues, MUC1 expression is relatively low and restricted to the apical surface of epithelial cells. However, in pathological conditions (especially tumors), its expression polarity is lost, and it is abnormally overexpressed on the entire cell surface.

Abnormal expression, aberrant glycosylation, and abnormal intracellular localization of MUC1 are closely associated with a variety of diseases, among which malignant tumors are the most extensively studied.
1) Tumors: MUC1 is overexpressed in various solid tumors, including breast cancer, lung cancer (especially non-small cell lung cancer), gastric cancer, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer, prostate cancer, ovarian cancer, and esophageal cancer. It is an independent prognostic factor for poor prognosis in breast cancer and is closely related to tumor invasion, metastasis, and immune escape. In tumor cells, abnormal expression of C1GALT1 and Cosmc leads to exposure of Tn and sTn antigens, which changes the conformation of MUC1 and promotes tumor progression. 2) Non-tumor diseases: MUC1 functional variants are also associated with cardiovascular metabolic indicators and renal function parameters, and may be involved in chronic inflammation and tissue fibrosis processes. It is also related to tubulointerstitial kidney disease (autosomal dominant 2) and renal cysts and diabetes syndrome.

Introduction of MUC1 Chimeric Antigen Receptor (CAR)

Chimeric Antigen Receptor (CAR) is a genetically engineered receptor that can redirect T cells (or other immune cells) to specifically recognize and kill target cells expressing specific antigens. MUC1, as a tumor-associated antigen (TAA) overexpressed in a variety of tumors, has become an important target for CAR-T cell therapy. MUC1 CAR-T cells can specifically recognize MUC1 (especially the cancer-associated abnormal glycosylation form of MUC1, such as Tn-MUC1) on the surface of tumor cells, thereby initiating an immune response and killing tumor cells, providing a new therapeutic strategy for the treatment of MUC1-positive tumors.

Similar to traditional CAR structures, MUC1 CAR is mainly composed of four core components, and its structure is continuously optimized with the development of generations.
1) Extracellular Antigen-Binding Domain: Usually a single-chain variable fragment (scFv) derived from a monoclonal antibody against MUC1, which can specifically bind to MUC1 (including the VNTR domain or the cancer-associated glycoform of MUC1). Some MUC1 CARs use camelid-derived VHH (variable domain of heavy chain antibodies) as the antigen-binding domain to improve binding specificity and stability.
2) Hinge Region: Connects the extracellular domain and the transmembrane domain, providing flexibility for the CAR structure, facilitating antigen binding, and reducing steric hindrance.
3) Transmembrane Domain: Anchors the CAR to the cell membrane of immune cells (such as T cells), ensuring the stability of the CAR structure.
4) Intracellular Signaling Domain: The core of CAR signal transduction, which determines the activation, proliferation, and survival of CAR-T cells. Different generations of MUC1 CARs differ mainly in the composition of the intracellular signaling domain.

MUC1 CAR Research Achievements

In recent years, MUC1 CAR research has made remarkable progress, with a large number of preclinical and clinical studies verifying its therapeutic potential in MUC1-positive tumors.
1) Preclinical Research: A variety of MUC1 CAR constructs have shown significant anti-tumor activity in xenograft models of various tumors. For example, engineered CAR-T cells targeting the cancer-associated Tn-glycoform of MUC1 demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. A second-generation VHH-based anti-MUC1 CAR, which contains a camelid-derived anti-MUC1 VHH followed by an IgG3 hinge, a CD28 transmembrane domain, and signaling endo domains of CD28 and CD3ζ, was successfully constructed and showed effective targeting of MUC1-positive cancer cells. In addition, MUC1 CAR-T cells constructed with lentiviral vectors (expressing scFv of anti-MUC1 antibody linked to 4-1BB and CD3ζ signaling domains) showed potential therapeutic effects in colorectal cancer models.
2) Clinical Research: At present, a number of MUC1 CAR-T cell therapy clinical trials are being carried out globally (such as NCT03525782, NCT05239143), mainly targeting non-small cell lung cancer, pancreatic cancer, breast cancer, and prostate cancer. Although no MUC1 CAR-T drugs have been officially approved yet, preliminary clinical data show that MUC1 CAR-T cells have good safety and certain anti-tumor efficacy in patients with advanced MUC1-positive tumors.

Marketed Drugs Targeting MUC1

At present, there are no marketed drugs specifically targeting MUC1 CAR, but a variety of MUC1-targeted drugs are in different stages of clinical research, covering CAR-T cell therapy, antibody-drug conjugates (ADC), cancer vaccines, etc. It should be noted that HDM2012, an injection developed by Huadong Medicine, is the world's first and currently only MUC17 ADC under research, which has shown good efficacy in PDX models of gastric cancer, colorectal cancer, and pancreatic cancer, but it targets MUC17 rather than MUC1. For MUC1-targeted therapies, most are in the clinical I/II stage, and it is expected that more MUC1-targeted drugs (including CAR-T) will be approved for marketing in the next few years, bringing new treatment options for patients with MUC1-positive tumors.

MUC1 CAR Research Hotspots

With the in-depth development of CAR technology, the research hotspots of MUC1 CAR are mainly focused on the following aspects.
1) Targeting Cancer-Associated Glycoforms of MUC1: Since MUC1 is also expressed in normal epithelial cells, targeting the cancer-associated abnormal glycosylation form of MUC1 (such as Tn-MUC1, sTn-MUC1) can improve the specificity of CAR-T cells, reduce off-target effects, and avoid damage to normal tissues. This has become a key research direction in MUC1 CAR research.
2) Optimization of CAR Structure: Developing high-generation MUC1 CARs (third, fourth, and fifth generations) to enhance the anti-tumor activity, persistence, and proliferation ability of CAR-T cells. For example, adding multiple co-stimulatory molecules (4-1BB, OX40, CD27) or cytokine signaling domains to improve the survival and anti-tumor efficacy of CAR-T cells in the tumor microenvironment.
3) Combination Therapy Strategies: Combining MUC1 CAR-T cell therapy with immune checkpoint inhibitors (PD-1/PD-L1 inhibitors), chemotherapy, radiotherapy, or targeted drugs to reverse the immunosuppressive tumor microenvironment, enhance the anti-tumor effect of CAR-T cells, and reduce tumor recurrence. For example, MUC1 CAR-T combined with PD-L1 inhibitors can effectively improve the infiltration and activation of CAR-T cells in tumors.
4) Application in Solid Tumors: Overcoming the bottleneck of CAR-T cell therapy in solid tumors, such as tumor infiltration, immunosuppressive microenvironment, and antigen heterogeneity. Exploring the application of MUC1 CAR-T cells in various solid tumors (such as pancreatic cancer, non-small cell lung cancer) and optimizing the delivery method of CAR-T cells to improve the therapeutic effect.
5) Multi-Target CAR Development: Developing multi-target CAR-T cells that simultaneously target MUC1 and other tumor-associated antigens (such as PSCA, EGFR, CEA) to solve the problem of tumor antigen heterogeneity and reduce the risk of tumor escape.

MUC1 CAR Research Difficulties & Challenges

Despite the great progress in MUC1 CAR research, there are still many difficulties and challenges that need to be solved.
1) Off-Target Effects: MUC1 is weakly expressed in normal epithelial cells. Although the expression level in tumors is significantly higher, CAR-T cells may still recognize and attack normal cells expressing MUC1, leading to side effects such as epithelial damage. How to improve the specificity of MUC1 CAR and reduce off-target effects is a key challenge.
2) Tumor Microenvironment (TME) Suppression: The immunosuppressive microenvironment of solid tumors (such as the presence of regulatory T cells, myeloid-derived suppressor cells, and immunosuppressive cytokines) can inhibit the activation, proliferation, and survival of MUC1 CAR-T cells, reducing their anti-tumor efficacy. How to reverse the immunosuppressive TME and enhance the function of MUC1 CAR-T cells is another major challenge.
3) Antigen Heterogeneity: The expression level and glycosylation pattern of MUC1 in different tumor patients, even in the same patient's tumor tissue, are different. This antigen heterogeneity may lead to tumor escape, making MUC1 CAR-T cells unable to completely eliminate tumor cells.
4) CAR-T Cell Persistence: In clinical studies, MUC1 CAR-T cells often show poor persistence in the body, which limits their long-term anti-tumor effect. How to improve the persistence of MUC1 CAR-T cells and maintain their long-term anti-tumor activity is an important research direction.
5) Safety Issues: Similar to other CAR-T cell therapies, MUC1 CAR-T cells may cause side effects such as cytokine release syndrome (CRS), neurotoxicity, and on-target off-tumor effects. How to effectively control these side effects and improve the safety of MUC1 CAR-T therapy is crucial for its clinical application.

References

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