PLA2G2D Antibody
Description
Mechanism of Action and Rationale
PLA2G2D is a calcium-dependent phospholipase that hydrolyzes phospholipids, modulating lipid mediators and immune cell activity . Key functions include:
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Immunosuppression: Suppresses dendritic cell function, inhibits T-cell activity, and promotes M2 macrophage polarization .
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Lipid Metabolism: Converts phosphatidylethanolamine (PE) into polyunsaturated fatty acids (PUFAs), which are precursors to anti-inflammatory resolvins (e.g., resolvin D1) .
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Tumor Microenvironment: High expression correlates with immune evasion and resistance to ICIs .
By blocking PLA2G2D, antibodies aim to restore anti-tumor immunity by:
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Enhancing T-cell activation: Reducing suppression of cytotoxic T cells.
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Promoting pro-inflammatory lipid mediators: Shifting the balance toward immune-activating signals.
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Synergy with ICIs: Overcoming resistance mechanisms in ICI-refractory tumors .
Antibody Generation and Selection
Apex Immune generated >700 monoclonal antibodies targeting PLA2G2D, narrowing candidates to 39 function-blocking antibodies through:
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Biochemical assays: Neutralization of enzymatic activity.
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Immune cell functional assays: Restoration of dendritic cell antigen presentation and T-cell proliferation .
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Top 5 candidates: Selected for efficacy in syngeneic tumor models and non-human primate toxicity studies .
| Parameter | Details |
|---|---|
| Antibody Source | Humanized mice (transgenic for PLA2G2D) |
| Target Validation | Does not cross-react with murine PLA2G2D |
| Syngeneic Models | Evaluated in melanoma, lung, and colon cancer models |
Efficacy in Preclinical Models
Anti-PLA2G2D antibodies demonstrated:
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Monotherapy efficacy: Tumor growth inhibition in syngeneic models .
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Combination synergy: Enhanced tumor regression when paired with anti-PD-1/PD-L1 therapies .
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Immune profile modulation: Increased intratumoral CD8+ T cells and reduced M2 macrophages .
PLA2G2D as a Prognostic Biomarker
Gene expression analyses in cutaneous squamous cell carcinoma (CSCC) revealed:
Source: Frontiers in Oncology (2021)
Immune Checkpoint Co-Expression
PLA2G2D expression is positively correlated with classical checkpoints:
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Co-expression suggests potential for combination therapies targeting multiple pathways.
Next-Generation Strategies
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Bispecific Antibodies: Combining PLA2G2D blockade with PD-1/PD-L1 inhibition.
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Biomarker-Driven Trials: Enriching for patients with high PLA2G2D expression.
Research Gaps and Opportunities
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Studies have shown that PLA2G2D expression is induced by various factors, including in mice and human monocyte-derived macrophages. (PMID: 26392224)
- sPLA(2)-IID is located in the head and midpiece of human sperm, and its activation is associated with acrosomal exocytosis. (PMID: 22240557)
- Phospholipid bilayer permeabilization by hsPLA2GIID is independent of its catalytic activity. (PMID: 22490726)
- The Gly80Ser polymorphism in PLA2G2D may be linked to body weight loss observed in chronic obstructive pulmonary disease (COPD) patients. PLA2G2D-Ser enhances the expression of IL-6 and IL-8 compared to PLA2G2D-Gly. (PMID: 19365107)
- TNF-alpha and IFN-gamma induce gene expression of a novel secretory PLA(2)IID in human airway epithelial cells. This suggests a potential role for PLA2G2D in cytokine-mediated inflammation in the respiratory tract. (PMID: 12396716)
- The GIID sPLA2 is clustered on human chromosome 1 and exhibits tissue-specific expression patterns, implying unique functional roles. (PMID: 15052324)
- Overexpression of human secretory phospholipase A2 group IIA leads to enhanced cholesterol delivery from phospholipolysed lipoproteins to the liver. (PMID: 15379211)
- Research indicates that sPLA2-IID might be a susceptibility gene contributing to body weight loss in COPD patients. (PMID: 16002569)
- Lipopolysaccharides inhibit interferon gamma-induced gene expression of secretory phospholipase A2 type IID in human monocyte-derived macrophages. (PMID: 16897354)
- The distribution pattern of sPLA2S in intact spermatozoa could serve as an additional parameter for evaluating sperm quality. (PMID: 18958346)
