FAP2 Antibody
Description
FAP2 Protein Overview
Fap2 is a 400 kDa outer membrane autotransporter protein that enables Fn to bind two targets:
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Gal-GalNAc: A tumor-associated glycan overexpressed in colorectal (CRC) and breast cancers .
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TIGIT: An inhibitory immune receptor on human natural killer (NK) and T cells .
This dual binding allows Fn to colonize tumors while suppressing immune cell activity, promoting cancer metastasis .
Mechanism of FAP2 in Immune Evasion
Structural studies reveal Fap2 adopts a 46.5 nm rod-shaped β-helix with distinct binding regions:
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TIGIT interaction: The tip of Fap2 binds TIGIT’s membrane-distal domain, inhibiting NK cell cytotoxicity .
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Gal-GalNAc interaction: A binding pit on Fap2’s β-helix facilitates tumor adhesion .
This dual functionality enables Fn to shield tumors from immune attack while anchoring to cancer cells .
Antibody Responses to FAP2 in Human Studies
Circulating and mucosal antibodies against Fap2 have been detected in humans:
Table 1: Antibody reactivity to Fn proteins in colorectal cancer patients
| Antigen | Controls (n=485) | Cases (n=485) | OR (95% CI) | P-value |
|---|---|---|---|---|
| Fn0131 | 9% | 6% | 0.61 (0.38–0.98) | 0.042 |
| Fn1426 | 10% | 11% | 1.06 (0.69–1.63) | 0.777 |
| Fn1817_1 | 10% | 8% | 0.82 (0.52–1.29) | 0.384 |
| Any protein | 53% | 47% | 0.81 (0.62–1.06) | 0.130 |
Salivary IgA antibodies targeting Fap2’s immunodominant region correlate with systemic IgG responses, suggesting mucosal and systemic immune coordination .
Therapeutic and Diagnostic Applications
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Immune reactivation: Blocking Fap2-TIGIT interaction restores NK cell activity in vitro .
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Cancer biomarkers: High Gal-GalNAc levels in breast tumors correlate with Fn colonization, detectable via Fap2-specific probes .
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Antibody engineering: Recombinant Fap2 produced in E. coli retains binding to TIGIT and Gal-GalNAc, enabling scalable antibody development .
Key Research Findings
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Breast cancer: Fap2-expressing Fn colonizes mammary tumors 1,000-fold more efficiently than Fap2-deficient strains .
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Lymphocyte apoptosis: Fap2 synergizes with RadD to induce Jurkat cell death, with double mutants reducing cytotoxicity by 95% .
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Structural insights: Cryo-EM resolved Fap2-TIGIT binding at 3.8 Å, guiding therapeutic antibody design .
Product Specs
Constituents: 50% Glycerol, 0.01M Phosphate Buffered Saline (PBS), pH 7.4
Target Background
Q&A
What is the Role of FAP2 in Cancer Research?
FAP2, an adhesin from Fusobacterium nucleatum, plays a crucial role in cancer research by facilitating bacterial attachment to cancer cells and immune cells. It interacts with the glycan Gal-GalNAc on cancer cells and the TIGIT receptor on immune cells, potentially impairing antitumor immune responses . This interaction can be studied using recombinant FAP2 expressed on Escherichia coli surfaces, which allows for the assessment of FAP2's role in tumor colonization .
How Can FAP2 Antibodies Be Utilized in Experimental Design?
FAP2 antibodies can be used in experimental designs to study the role of Fusobacterium nucleatum in cancer progression. For example, these antibodies can be employed in ELISA assays to measure circulating or salivary antibody levels against FAP2, providing insights into immune responses against F. nucleatum . Additionally, FAP2 antibodies can be used to block FAP2-mediated interactions in cell culture models, helping to elucidate the mechanisms by which F. nucleatum influences tumor microenvironments.
What Are the Challenges in Analyzing Data Contradictions Related to FAP2 Antibody Studies?
Analyzing data contradictions in FAP2 antibody studies involves addressing discrepancies in antibody reactivity across different sample types (e.g., plasma vs. saliva) and populations. For instance, studies may show varying levels of correlation between circulating and salivary antibodies to FAP2, which could be due to differences in sample collection methods or population demographics . Researchers must consider these factors when interpreting results and designing follow-up studies to resolve inconsistencies.
How Can FAP2 Antibodies Be Used in Advanced Research Scenarios?
In advanced research scenarios, FAP2 antibodies can be used to develop targeted therapies against Fusobacterium nucleatum in cancer. For example, by blocking FAP2 interactions with cancer cells, researchers can explore whether reducing bacterial attachment impacts tumor growth or metastasis. Additionally, FAP2 antibodies can be utilized in combination with other treatments, such as antibiotics or immunotherapies, to enhance their efficacy in cancer models .
What Methodological Approaches Are Recommended for Detecting FAP2 Antibodies?
Detecting FAP2 antibodies involves using sensitive and specific methods such as ELISA or Western blotting. For ELISA, competitive assays can be employed to assess antibody reactivity against FAP2 mimotopes . Additionally, CRISPR-based methods can be used for rapid and sensitive detection of bacterial components associated with FAP2 in clinical samples .
How Do FAP2 Antibodies Interact with Other Bacterial Components in Cancer Research?
FAP2 antibodies interact with other bacterial components by targeting specific adhesins that facilitate bacterial attachment to host cells. In the context of Fusobacterium nucleatum, FAP2 is a key factor that allows the bacteria to colonize tumors. Other bacteria, such as Selenomonas, Bacteroides, and Prevotella, may also be present and influence the tumor microenvironment, potentially interacting with FAP2 or other adhesins .
What Are the Implications of FAP2 Antibodies for Cancer Diagnosis and Treatment?
FAP2 antibodies have implications for cancer diagnosis by potentially serving as biomarkers for Fusobacterium nucleatum infections associated with tumors. In treatment, targeting FAP2 could disrupt bacterial colonization of tumors, enhancing the effectiveness of conventional therapies. Additionally, understanding FAP2's role in immune modulation could inform strategies to restore antitumor immunity .
How Can Structural Analysis of FAP2 Inform Antibody Development?
Structural analysis of FAP2, such as cryo-EM studies, reveals its rod-shaped structure and specific binding sites for Gal-GalNAc and TIGIT . This information can guide the development of antibodies that specifically target these interaction sites, potentially blocking FAP2-mediated bacterial attachment to cancer cells and immune cells.
What Are the Challenges in Developing Therapeutic Antibodies Against FAP2?
Developing therapeutic antibodies against FAP2 involves challenges such as ensuring specificity to avoid off-target effects and achieving sufficient affinity to effectively block FAP2 interactions in vivo. Additionally, the potential for FAP2-negative strains of Fusobacterium nucleatum requires consideration in therapeutic strategies .
How Can FAP2 Antibodies Be Integrated into Multimodal Cancer Therapies?
FAP2 antibodies can be integrated into multimodal cancer therapies by combining them with antibiotics, immunotherapies, or chemotherapy. For example, targeting FAP2 to reduce bacterial colonization could enhance the efficacy of checkpoint inhibitors by restoring immune function against tumors . This approach requires careful consideration of treatment sequencing and dosing to maximize synergistic effects.
Data Table Example: FAP2 Antibody Reactivity
| Sample Type | Antibody Reactivity to FAP2 | Correlation with Cancer Status |
|---|---|---|
| Plasma | High IgG levels | Positive correlation with CRC |
| Saliva | High IgA levels | Positive correlation with oral infections |
| Tissue | Variable reactivity | Requires further investigation |
