Customize HSD5 Antibody

Description

Target Profile and Development

EphA2 is a transmembrane receptor implicated in tumor progression, metastasis, and chemotherapy resistance. In PDAC, EphA2 overexpression correlates with poor prognosis due to its role in activating survival pathways such as AKT, ERK, FAK, and STAT3 . The hSD5 antibody was developed using phage display technology, targeting a discontinuous epitope on EphA2’s active site to block ligand-independent signaling .

Key Attributes of hSD5:

Property	Description
Target	EphA2 receptor
Format	Humanized IgG1 monoclonal antibody
Mechanism	Induces EphA2 endocytosis and degradation; inhibits Ras-MAPK/STAT3 pathways
Therapeutic Applications	Pancreatic cancer, other EphA2-positive malignancies

Mechanism of Action

hSD5 binds EphA2 with high specificity, triggering two primary antitumor effects:

Receptor Degradation: Internalization and lysosomal degradation of EphA2, reducing cell-surface receptor levels .
Pathway Inhibition: Suppression of phosphorylated AKT, ERK, FAK, and STAT3, critical for tumor proliferation and migration .
Synergy with Chemotherapy: Enhances gemcitabine efficacy by overcoming EphA2-mediated drug resistance .

In Vitro and In Vivo Findings

Cell Lines Tested: BxPc-3 and Mia PaCa-2 (pancreatic cancer) .
Monotherapy: Reduced tumor growth by 60–70% in xenograft models .
Combination with Gemcitabine: Achieved 85–90% tumor suppression, surpassing either agent alone .

Antibody-Drug Conjugate (ADC) Development

To amplify potency, hSD5 was conjugated to monomethyl auristatin E (MMAE), forming the ADC hSD5-vedotin :

Parameter	hSD5-Vedotin Performance
Payload	MMAE (microtubule disruptor)
Target Binding	Retains EphA2 specificity
In Vitro IC50	Sub-nanomolar range in PDAC cell lines
In Vivo Efficacy	Complete tumor regression in xenograft models
Resistance Observation	Immune-mediated resistance in recurrent tumors

Clinical Potential and Challenges

Advantages:
- Dual action: EphA2 degradation + payload delivery (in ADC format).
- Broad applicability to EphA2-overexpressing cancers (e.g., lung, ovarian) .
Challenges:
- Risk of antigen escape in recurrent tumors .
- Requires biomarker-driven patient stratification for optimal response.

Future Directions

Clinical Trials: Phase I studies are pending to evaluate safety and dosing .
Combination Strategies: Pairing with immune checkpoint inhibitors to counteract resistance .
Multispecific Formats: Bispecific antibodies targeting EphA2 and complementary antigens (e.g., PD-L1) could enhance efficacy .

Product Specs

Buffer

Preservative: 0.03% ProClin 300; Constituents: 50% Glycerol, 0.01M Phosphate-Buffered Saline (PBS), pH 7.4

Form

Liquid

Lead Time

14-16 week lead time (made-to-order)

Synonyms

HSD5 antibody; At4g10020 antibody; T5L19.150 antibody; 11-beta-hydroxysteroid dehydrogenase-like 5 antibody; EC 1.1.1.- antibody; 17-beta-hydroxysteroid dehydrogenase-like 5 antibody; EC 1.1.1.- antibody; Hydroxysteroid dehydrogenase 5 antibody; AtHSD5 antibody

Target Names

HSD5

Uniprot No.

Q9T0G0

Target Background

Database Links

KEGG: ath:AT4G10020

STRING: 3702.AT4G10020.1

UniGene: At.33656

Protein Families

Short-chain dehydrogenases/reductases (SDR) family

Subcellular Location

Membrane; Single-pass type II membrane protein.

Q&A

Here’s a structured collection of FAQs tailored for academic researchers working with HSD5 antibody, incorporating methodological guidance and research insights from the provided sources:

Advanced Research Questions

How does HSD5’s CDRH3 domain mediate EphA2 interaction?

Structural analysis workflow:
- Solve the crystal structure of HSD5 Fab bound to EphA2 extracellular domain .
- Perform alanine scanning mutagenesis on CDRH3 residues to identify critical binding motifs .
- Use molecular docking simulations to predict energetic contributions of key residues (e.g., hydrophobic vs. polar interactions) .
Key findings:
CDRH3 forms a β-sheet interface with EphA2’s ligand-binding domain, with residues Tyr95 and Arg97 critical for affinity .

What strategies improve HSD5’s therapeutic efficacy in antibody-drug conjugates (ADCs)?

Engineering approaches:
- Linker optimization: Test cleavable (e.g., Val-Cit) vs. non-cleavable linkers for MMAE payload release .
- Humanization: Replace murine FR regions with human germline sequences while retaining CDR integrity .
- Affinity maturation: Use phage display to enhance EphA2 binding (KD ≤ nM range) .

How to evaluate HSD5-vedotin’s tumor-killing mechanism in vivo?

Preclinical model design:
- Establish pancreatic cancer xenografts in immunodeficient mice .
- Monitor tumor volume and apoptosis markers (e.g., cleaved caspase-3) post-treatment.
- Track ADC internalization via fluorescently labeled HSD5 and quantify MMAE release via LC-MS .

Data Contradiction Analysis

Why does HSD5-vedotin show reduced efficacy in recurrent tumors?

Hypotheses and validation:

Factor	Analysis Method	Source
Immune resistance	Flow cytometry for T-cell infiltration
EphA2 downregulation	IHC and RNA-seq of recurrent vs. primary tumors
ADC clearance	Pharmacokinetic studies with radiolabeled HSD5

Solutions:
- Combine with immune checkpoint inhibitors (e.g., anti-PD-1) .
- Develop bispecific ADCs targeting EphA2 and compensatory pathways .

Methodological Tables

Epitope Mapping Techniques for HSD5:

Method	Resolution	Throughput	Advantages
X-ray crystallography	Atomic (Å)	Low	Reveals structural determinants
Hydrogen-deuterium exchange	Peptide-level	Medium	Maps solvent-accessible regions
SPR mutagenesis	Residue-level	High	Quantifies binding energy contributions

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HSD5 Antibody