MUC21 Antibody

What is MUC21 and why is it important in cancer research?

MUC21 is a transmembrane mucin glycoprotein that plays multiple roles in cancer biology. Recent CRISPR activation screens have identified MUC21 as a critical cell surface molecule that inhibits NK cell cytotoxicity and antibody-dependent cellular cytotoxicity . MUC21 creates steric hindrance that prevents interactions between cancer cells and immune cells, thereby facilitating immune evasion . Additionally, MUC21 promotes cancer cell viability and migration in glioblastoma via the STAT3/AKT pathway . Its expression is elevated in various cancers, including lung cancer and glioblastoma, where it correlates with decreased immune cell infiltration and reduced responsiveness to anti-PD-(L)1 immunotherapy . These findings position MUC21 as a potential therapeutic target for enhancing cancer immunotherapy efficacy.

What types of MUC21 antibodies are available for research purposes?

Several types of MUC21 antibodies have been developed for research applications:

• Monoclonal antibodies (mAbs): Specific mAbs like heM21C and heM21D have been generated using human embryonic kidney 293 cells transfected with MUC21 as the immunogen . These mAbs show differential binding to glycosylated forms of MUC21:

  • heM21D binds to both the unmodified core polypeptide and Tn-MUC21 (MUC21 with N-acetylgalactosamine)

  • heM21C binds to MUC21 with Tn, T, or sialyl-T epitopes but not to the unmodified core polypeptide

• Polyclonal antibodies: These recognize broader epitope ranges on MUC21, such as the polyclonal antibody targeting amino acids 505-566 of human MUC21 .

The choice between these antibody types depends on the specific research application and whether detection of particular glycoforms is required.

What are the recommended applications for MUC21 antibodies in laboratory research?

MUC21 antibodies can be utilized in multiple research applications:

• Western blotting: For detecting MUC21 protein expression in cell or tissue lysates

• Immunohistochemistry: For both frozen and paraffin-embedded tissue sections to visualize MUC21 localization and expression patterns

• Immunocytochemistry: For cellular localization studies

• Flow cytometry: For detecting MUC21 expression on cell surfaces

• ELISA: For quantitative measurement of MUC21 levels

• Immunoprecipitation: For isolating MUC21 protein complexes

• ADCC assays: For studying antibody-dependent cellular cytotoxicity in the context of MUC21 expression

When selecting an antibody for these applications, consider the specific epitope recognition properties, as this affects the detection of different MUC21 glycoforms.

How should researchers validate MUC21 antibody specificity in their experimental systems?

Validating MUC21 antibody specificity is crucial for obtaining reliable research results. A comprehensive validation approach should include:

• Positive and negative controls:

  • Use cell lines with known MUC21 expression (e.g., NCI-H441 lung cancer cells) as positive controls

  • Use MUC21-knockout or knockdown cells (via CRISPR or shRNA) as negative controls

  • Consider using variant Chinese hamster ovary (CHO) cells (ldlD, Lec2) with different glycosylation capabilities to validate glycoform-specific antibodies

• Multiple detection methods:

  • Compare results from at least two independent methods (e.g., Western blot and immunohistochemistry)

  • Perform immunoprecipitation followed by mass spectrometry for definitive protein identification

• Peptide competition assays:

  • Pre-incubate antibody with purified MUC21 peptide to demonstrate signal elimination in positive samples

• Differential glycosylation analysis:

  • For glycoform-specific antibodies, test on cells with modulated glycosylation (e.g., using glycosylation inhibitors or CHO cell variants)

A systematic validation using these approaches ensures reliable antibody performance in subsequent experiments.

What factors affect MUC21 detection in clinical and research samples?

Several factors can influence the detection of MUC21 in experimental and clinical samples:

• Glycosylation status: MUC21 undergoes extensive O-glycosylation, which can mask epitopes or create new ones. Different antibodies recognize specific glycoforms of MUC21, so detection varies based on glycosylation patterns .

• Tissue fixation methods: For immunohistochemistry, the fixation method significantly impacts MUC21 epitope preservation. Formalin fixation may cross-link proteins and mask epitopes, requiring appropriate antigen retrieval methods .

• Expression levels: MUC21 expression varies across tissue types and disease states. Higher expression has been observed in lung cancer and glioblastoma compared to normal tissues .

• Sample preparation: Protein extraction methods can affect MUC21 recovery, especially due to its transmembrane nature. Specialized lysis buffers containing appropriate detergents are recommended.

• Disease state: MUC21 glycoforms change during carcinogenesis. In esophageal squamous carcinoma cells, MUC21 is produced without O-glycan attachment, which differs from normal squamous epithelia .

Researchers should account for these factors when designing experiments and interpreting results involving MUC21 detection.

What are the optimal conditions for using MUC21 antibodies in immunohistochemistry?

For optimal immunohistochemical detection of MUC21, consider the following protocol recommendations:

• Tissue fixation and processing:

  • For formalin-fixed paraffin-embedded (FFPE) tissues: 10% neutral-buffered formalin fixation for 24-48 hours

  • For frozen sections: OCT embedding and snap-freezing in liquid nitrogen

• Antigen retrieval:

  • Heat-induced epitope retrieval (HIER) using citrate buffer (pH 6.0) or EDTA buffer (pH 9.0)

  • Optimize retrieval time (typically 15-20 minutes) for specific antibodies

• Blocking and antibody incubation:

  • Block with 3-5% BSA or normal serum from the species of secondary antibody

  • Primary antibody dilutions should be optimized (typically 1:100 to 1:500)

  • Incubate at 4°C overnight for maximum sensitivity

• Detection system:

  • For weakly expressed MUC21, amplification systems like tyramide signal amplification may improve sensitivity

  • Use appropriate controls for glycoform-specific antibodies, as differential staining patterns may be observed

• Counterstaining and mounting:

  • Light hematoxylin counterstaining for better visualization of MUC21 membranous staining

  • Use aqueous mounting medium if fluorescence detection is employed

These conditions should be optimized for each specific MUC21 antibody and tissue type to ensure reliable and reproducible results.

How can MUC21 antibodies be used to study cancer immune evasion mechanisms?

MUC21 antibodies are valuable tools for investigating cancer immune evasion mechanisms:

• Blocking antibody experiments:

  • Use neutralizing anti-MUC21 antibodies in co-culture systems with cancer cells and immune cells (NK or T cells) to assess the direct role of MUC21 in immune suppression

  • Measure changes in immune cell cytotoxicity, cytokine production, and immune synapse formation

• Combination with immune checkpoint inhibitors:

  • Test MUC21 antibodies in combination with anti-PD-L1 or other checkpoint inhibitors to evaluate potential synergistic effects

  • Assess T cell activation and tumor cell killing in vitro and in vivo

• Imaging immune interactions:

  • Use fluorescently labeled MUC21 antibodies for live cell imaging to visualize immune cell-cancer cell interactions

  • Quantify contact duration, immune synapse formation, and effector molecule polarization

• Therapeutic potential assessment:

  • Develop and test antibody-drug conjugates targeting MUC21 for selective delivery of cytotoxic agents to cancer cells

  • Evaluate the efficacy of MUC21-targeted CAR-T approaches

Research findings indicate that MUC21 expression on cancer cell surfaces inhibits both NK cell cytotoxicity and antibody-dependent cellular cytotoxicity by creating steric hindrance that prevents effective immune cell engagement . Targeting MUC21 with specific antibodies could potentially overcome this immune evasion mechanism.

What role does glycosylation play in MUC21 antibody binding and function?

Glycosylation significantly influences MUC21 antibody binding and biological function:

• Antibody epitope accessibility:

  • O-glycosylation can mask or create epitopes on MUC21, affecting antibody binding

  • Different antibodies recognize specific glycoforms: some bind only to glycosylated MUC21 (e.g., heM21C recognizes MUC21 with Tn, T, or sialyl-T epitopes), while others (e.g., heM21D) bind to both glycosylated and unglycosylated forms

• Functional implications:

  • Glycosylation status of MUC21 affects its biological functions, including resistance to apoptosis

  • Sialylated T-antigen and nonsialylated T-antigen on MUC21 both confer resistance to etoposide-induced apoptosis

  • O-glycan attachment is essential for MUC21's antiapoptotic effects, as demonstrated in CHO cell variant (ldlD cells) experiments

• Tissue-specific glycosylation:

  • In normal esophageal squamous epithelia, MUC21 carries extended O-glycans, while in esophageal squamous carcinoma cells, MUC21 lacks O-glycan attachment

  • This differential glycosylation can be detected using glycoform-specific antibodies, providing diagnostic potential

• Experimental approach to studying glycosylation effects:

  • Use CHO cell variants with defined glycosylation defects:

    • CHO-K1 (wild-type): Complete glycosylation

    • Lec2: Lacking sialylation

    • ldlD: Defective in both N- and O-glycosylation unless supplemented with specific sugars

Understanding the relationship between MUC21 glycosylation and antibody binding is crucial for developing effective diagnostic and therapeutic approaches targeting this mucin.

How can MUC21 antibodies be utilized in cancer diagnostics and prognostics?

MUC21 antibodies show significant potential for cancer diagnostics and prognostics:

• Differential diagnosis:

  • MUC21 antibodies that distinguish between glycoforms can differentiate normal and malignant tissues

  • In esophageal tissue, mAb heM21D (binding to unglycosylated MUC21) shows reactivity in carcinoma cells, while mAb heM21C (binding to glycosylated MUC21) is negative in carcinoma but positive in normal squamous epithelia

• Prognostic biomarker development:

  • High MUC21 expression correlates with reduced immune cell infiltration in lung cancer

  • MUC21 expression is associated with tumor recurrence in glioblastoma patients

  • MUC21 expression is higher in non-small cell lung cancer tumors that do not respond to anti-PD-(L)1 treatment

• Predictive biomarker for immunotherapy response:

  • Multiplex immunohistochemistry combining MUC21 antibodies with immune cell markers could help predict response to immunotherapy

  • Analysis of MUC21 expression and glycosylation patterns before and during treatment might monitor therapeutic efficacy

• Liquid biopsy applications:

  • Detection of circulating MUC21 or MUC21-expressing exosomes in patient blood samples

  • Correlation of these biomarkers with disease progression and treatment response

A combined approach using glycoform-specific MUC21 antibodies and comprehensive tissue analysis could enhance cancer diagnosis and treatment stratification.

What are the most effective protocols for generating MUC21-specific monoclonal antibodies?

Generating high-quality MUC21-specific monoclonal antibodies requires careful consideration of antigen design and screening strategies:

• Antigen preparation strategies:

  • Whole cell immunization: Use MUC21-transfected human embryonic kidney 293 cells as immunogen

  • Recombinant protein approach: Express and purify specific domains of MUC21 (e.g., amino acids 505-566)

  • Synthetic peptide approach: Design peptides based on predicted immunogenic epitopes of MUC21, considering both glycosylated and non-glycosylated regions

• Immunization and hybridoma production:

  • Multiple immunization rounds with purified antigen or MUC21-expressing cells

  • Fusion of spleen cells with myeloma cells to generate hybridomas

  • Screen hybridoma supernatants against different glycoforms of MUC21

• Antibody screening strategy:

  • Primary screening: ELISA against recombinant MUC21 or MUC21-expressing cells

  • Secondary validation: Flow cytometry of MUC21-positive and negative cell lines

  • Specificity confirmation: Western blotting, immunoprecipitation, and immunohistochemistry

  • Glycoform specificity assessment: Test antibody binding to MUC21 expressed in CHO cell variants with different glycosylation capabilities (CHO-K1, Lec2, ldlD cells)

• Epitope mapping and characterization:

  • Define binding epitopes using truncated MUC21 constructs or peptide arrays

  • Characterize glycoform specificity using glycosylation inhibitors or enzymatic deglycosylation

  • Assess functional properties (neutralizing capacity, ADCC induction)

Following these approaches has successfully yielded antibodies like heM21C and heM21D that recognize different glycoforms of MUC21 and can differentiate between normal and malignant tissues .

How should researchers optimize Western blotting protocols for MUC21 detection?

Detecting MUC21 by Western blotting requires specific optimizations due to its glycosylation and transmembrane nature:

• Sample preparation:

  • Lysis buffer: Use RIPA buffer supplemented with 1% Triton X-100 or NP-40 for effective membrane protein extraction

  • Protease inhibitors: Include complete protease inhibitor cocktail to prevent degradation

  • Phosphatase inhibitors: Add if studying phosphorylated forms of MUC21

  • Denaturation: Heat samples at 95°C for 5 minutes in Laemmli buffer with DTT or β-mercaptoethanol

• Gel electrophoresis considerations:

  • Use 6-8% SDS-PAGE gels for better resolution of high molecular weight glycosylated MUC21

  • Consider gradient gels (4-15%) if analyzing both glycosylated and non-glycosylated forms

  • Extended running time may be necessary for proper separation

• Transfer optimizations:

  • Use PVDF membranes (0.45 μm pore size) for better binding of high molecular weight proteins

  • Wet transfer at low voltage (30V) overnight at 4°C improves transfer efficiency

  • Add 0.1% SDS to transfer buffer to enhance transfer of glycoproteins

• Blocking and antibody incubation:

  • Block with 5% non-fat dry milk in TBST (may need optimization depending on antibody)

  • For phospho-specific detection, use 5% BSA instead of milk

  • Primary antibody dilution: Start with 1:1000 and optimize as needed

  • Incubate primary antibody overnight at 4°C for maximum sensitivity

• Detection considerations:

  • Enhanced chemiluminescence (ECL) systems with longer exposure times may be necessary

  • For quantitative analysis, consider fluorescent secondary antibodies and imaging systems

• Controls and validation:

  • Include positive control (MUC21-expressing cell line) and negative control (knockdown cells)

  • Consider deglycosylation treatments to confirm glycoprotein identity:

    • PNGase F for N-glycans

    • O-glycosidase plus neuraminidase for O-glycans

These optimizations will help ensure reliable detection of MUC21 in Western blotting applications.

What are the key considerations for using MUC21 antibodies in flow cytometry?

For effective flow cytometric analysis of MUC21 expression, researchers should consider:

• Cell preparation:

  • Gentle dissociation methods to preserve cell surface epitopes (e.g., non-enzymatic cell dissociation solution or mild trypsin treatment)

  • Fixation: If required, use 2-4% paraformaldehyde for 10-15 minutes at room temperature

  • Permeabilization: Only if detecting intracellular domains (0.1% saponin or 0.1% Triton X-100)

• Staining protocol optimization:

  • Blocking: Use 5% normal serum (from secondary antibody species) or 1% BSA to reduce non-specific binding

  • Primary antibody concentration: Titrate antibodies (typically 1-10 μg/ml) to determine optimal concentration

  • Incubation conditions: 30-60 minutes on ice for surface staining

  • Washing: Multiple gentle washes with PBS containing 0.5-1% BSA

• Antibody selection considerations:

  • Choose antibodies validated for flow cytometry

  • Consider glycoform specificity - different antibodies may recognize specific glycoforms of MUC21

  • For multicolor panels, select appropriate fluorophores considering your cytometer configuration and other markers in the panel

• Controls:

  • Isotype controls matched to primary antibody

  • Unstained cells for autofluorescence assessment

  • Single-stained controls for compensation

  • Positive controls: Cell lines with known MUC21 expression (e.g., NCI-H441)

  • Negative controls: MUC21 knockdown cells or cells known to be negative for MUC21

• Data analysis recommendations:

  • Gate on viable cells using appropriate viability dye

  • Analyze MUC21 expression as mean fluorescence intensity (MFI) rather than just percent positive

  • Consider bimodal distributions that may represent different glycoforms or expression levels

Following these guidelines will enable accurate assessment of MUC21 expression on cell surfaces by flow cytometry.

How does MUC21 expression correlate with immune cell infiltration in cancer?

Research findings demonstrate significant correlations between MUC21 expression and immune cell infiltration in cancer tissues:

• Inverse correlation with cytotoxic immune cells:

  • Bioinformatics analysis reveals that elevated MUC21 expression in lung cancer correlates with reduced infiltration and activation of cytotoxic immune cells

  • This suggests MUC21 contributes to an immunosuppressive tumor microenvironment

• Impact on immunotherapy response:

  • MUC21 expression is higher in non-small cell lung cancer (NSCLC) tumors that do not respond to anti-PD-(L)1 treatment compared to responsive tumors

  • This indicates MUC21 may be a biomarker for immunotherapy resistance and a potential target for combination therapy

• Mechanism of immune suppression:

  • MUC21 creates steric hindrance that prevents effective interactions between cancer cells and immune cells

  • This physical barrier inhibits formation of immune synapses and subsequent cytotoxic responses

  • MUC21 expression hinders T cell activation by impeding antigen recognition

• Effects on different immune cell types:

  • Inhibits NK cell cytotoxicity

  • Reduces antibody-dependent cellular cytotoxicity

  • Diminishes T cell activation and effectiveness of immune checkpoint inhibitors

  • Suppresses antitumor function of both CAR-T cells and CAR-NK cells

These findings suggest that MUC21 antibodies could be valuable tools for studying tumor-immune interactions and potentially for developing combination immunotherapy approaches.

What is the relationship between MUC21 glycosylation and cancer cell apoptosis resistance?

MUC21 glycosylation plays a critical role in conferring resistance to apoptosis in cancer cells:

• O-glycosylation dependency:

  • MUC21 transfection into HEK293 cells decreases apoptotic cell numbers in response to etoposide treatment or ultraviolet light irradiation

  • This antiapoptotic effect is dependent on the glycosylation status of MUC21

• Specific glycan structures required:

  • Experiments with CHO cell variants revealed that T-antigen (with or without sialic acid) is essential for MUC21's antiapoptotic effect

  • MUC21 expressing sialyl T-antigen in CHO-K1 cells confers resistance to etoposide-induced apoptosis

  • MUC21 with nonsialylated T-antigen in Lec2 cells also provides apoptosis resistance

• Experimental evidence from ldlD cells:

  • When MUC21 was transfected into ldlD cells (defective in both N- and O-glycosylation):

    • Nonsupplemented cells showed no resistance to etoposide-induced apoptosis

    • Cells supplemented with only N-acetylgalactosamine showed no resistance

    • Cells supplemented with both N-acetylgalactosamine and galactose (expressing sialyl T-antigen) exhibited resistance to etoposide-induced apoptosis

• Mechanism independent of galectin-3:

  • Galectin-3 knockdown in MUC21-transfected HEK293 cells did not significantly affect MUC21-dependent induction of apoptosis resistance

  • This suggests that MUC21's antiapoptotic effect operates through other molecular mechanisms

These findings indicate that specific glycan structures on MUC21 are essential for its role in promoting cancer cell survival, which could inform the development of targeted therapies.

How can MUC21 antibodies be used to improve cancer immunotherapy approaches?

MUC21 antibodies hold significant potential for enhancing cancer immunotherapy strategies:

• Overcoming immune evasion mechanisms:

  • Blocking antibodies against MUC21 could disrupt its immunosuppressive effects, enhancing NK and T cell access to cancer cells

  • Anti-MUC21 antibodies may remove the steric hindrance that prevents immune cell-cancer cell interactions

• Combination therapy approaches:

  • Using anti-MUC21 antibodies alongside immune checkpoint inhibitors (anti-PD-1/PD-L1) could improve response rates

  • MUC21 expression is higher in non-responders to anti-PD-(L)1 therapy, suggesting MUC21 as a resistance mechanism

  • Potential synergistic effects by targeting multiple immune evasion pathways simultaneously

• Antibody-drug conjugates (ADCs):

  • Developing ADCs targeting MUC21 could deliver cytotoxic payloads specifically to MUC21-expressing cancer cells

  • Differential glycosylation between normal and cancer tissues provides tumor specificity

• CAR-T/NK cell therapy enhancement:

  • MUC21 suppresses antitumor function of both CAR-T cells and CAR-NK cells

  • Anti-MUC21 strategies could potentially improve CAR-T/NK efficacy

  • Alternative approach: developing CAR-T/NK cells targeting MUC21 directly

• Diagnostic companion applications:

  • Use glycoform-specific MUC21 antibodies to identify patients likely to benefit from anti-MUC21 therapeutic approaches

  • Monitor treatment response by assessing changes in MUC21 expression or glycosylation

The development of therapeutically effective anti-MUC21 antibodies could represent a promising strategy to improve cancer immunotherapy, particularly for patients who do not respond to current approaches.

What are the emerging technologies for studying MUC21 interactions with the immune system?

Several cutting-edge technologies are being applied to study MUC21's role in immune evasion:

• Advanced imaging techniques:

  • Super-resolution microscopy to visualize MUC21 distribution on cancer cell surfaces

  • Live-cell imaging with labeled MUC21 antibodies to track dynamic interactions with immune cells

  • Lattice light-sheet microscopy for 3D visualization of immune synapses in the presence of MUC21

• Single-cell analysis approaches:

  • Single-cell RNA-seq to correlate MUC21 expression with immune signatures in tumors

  • CyTOF (mass cytometry) to simultaneously measure MUC21 and immune cell markers in tissue samples

  • Spatial transcriptomics to map MUC21 expression relative to immune cell locations in the tumor microenvironment

• Proteomics and glycomics:

  • Glycoproteomics to characterize site-specific glycosylation patterns of MUC21

  • Proximity labeling (BioID, APEX) to identify MUC21 interaction partners

  • Cross-linking mass spectrometry to detect direct protein-protein interactions

• Functional screening platforms:

  • CRISPR activation/knockout screens to identify regulatory factors of MUC21 expression and glycosylation

  • Glycosyltransferase engineering to create specific glycoforms of MUC21

  • High-throughput antibody screening against different MUC21 glycoforms

• In vivo imaging and analysis:

  • Intravital microscopy to visualize immune interactions with MUC21-expressing tumors

  • Multiplexed immunofluorescence to assess MUC21 and immune markers in patient samples

  • PET imaging with radiolabeled anti-MUC21 antibodies for non-invasive tumor assessment

These technologies will help elucidate the complex mechanisms by which MUC21 modulates immune responses in cancer and identify optimal therapeutic strategies.

What are the challenges in developing MUC21-targeted therapeutic antibodies?

Developing effective therapeutic antibodies against MUC21 faces several challenges:

• Glycosylation heterogeneity:

  • MUC21 displays variable glycosylation patterns across different tissues and disease states

  • Selecting optimal epitopes that are accessible regardless of glycosylation or specifically target cancer-associated glycoforms is challenging

  • Glycoform-specific antibodies may have limited applicability across different cancer types

• Functional blocking requirements:

  • Identifying epitopes that, when bound by antibodies, functionally block MUC21's immunosuppressive effects

  • Need for antibodies that can penetrate the glycocalyx barrier to reach membrane-proximal domains

• Potential on-target/off-tumor effects:

  • MUC21 is expressed in normal tissues, including esophageal squamous epithelia

  • Antibodies must selectively target cancer-specific MUC21 variants to minimize toxicity

  • Differential glycosylation between normal and malignant tissues provides a potential targeting strategy

• Technical production challenges:

  • Generating antibodies against heavily glycosylated proteins can be technically difficult

  • Maintaining consistent glycoform recognition in manufactured antibody batches

  • Validation of functional activity across diverse experimental systems

• Combination therapy considerations:

  • Determining optimal combinations with existing immunotherapies

  • Identifying predictive biomarkers for patient selection

  • Understanding resistance mechanisms that might emerge

Addressing these challenges will be crucial for successful clinical translation of MUC21-targeted therapeutic approaches.

How might MUC21 antibodies be integrated into multimodal cancer therapy approaches?

MUC21 antibodies could enhance multimodal cancer therapy through several strategic approaches:

• Rational combination with immune checkpoint inhibitors:

  • Sequential therapy: Anti-MUC21 treatment followed by anti-PD-(L)1 therapy

  • Concurrent administration to simultaneously target multiple immune evasion mechanisms

  • Patient stratification based on MUC21 expression levels to identify optimal candidates for combination therapy

• Integration with conventional treatments:

  • Combining with chemotherapy: MUC21 confers resistance to apoptosis , so targeting it might enhance chemosensitivity

  • Radiation therapy combinations: Radiation can increase tumor antigen presentation, which might be more effective when MUC21-mediated immune evasion is blocked

  • Surgical adjuvant therapy: Post-surgical anti-MUC21 treatment to eliminate microscopic residual disease

• Advanced antibody engineering approaches:

  • Bispecific antibodies targeting both MUC21 and immune activating receptors (e.g., CD3, CD16)

  • Antibody-drug conjugates delivering cytotoxic payloads to MUC21-expressing cancer cells

  • Radioimmunotherapy using radiolabeled anti-MUC21 antibodies

• Cell therapy enhancement:

  • Pre-treatment with anti-MUC21 antibodies before CAR-T/NK cell therapy to improve tumor access

  • Engineering CAR-T cells that simultaneously target MUC21 and another tumor antigen

  • Combining with NK cell therapy to overcome MUC21-mediated inhibition of NK cytotoxicity

• Personalized approach based on MUC21 glycosylation:

  • Using glycoform-specific antibodies to target cancer-specific MUC21 variants

  • Monitoring glycosylation changes during treatment as a biomarker of response

  • Adapting therapy based on glycosylation profile evolution

These integrated approaches could significantly enhance the efficacy of cancer therapy by overcoming MUC21-mediated immune evasion and resistance mechanisms.