pat-6 Antibody
Description
Target and Mechanism of Action
PAT-SM6 binds to a conformational epitope of GRP78 exposed on the surface of malignant cells. GRP78 plays a role in the unfolded protein response (UPR) and is linked to drug resistance and poor prognosis in cancer . Key mechanisms include:
Primary Mechanisms
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Apoptosis induction: Internalization of oxidized low-density lipoprotein (LDL) bound to GRP78 triggers intracellular cholesterol accumulation, activating caspase-dependent apoptosis .
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Complement-dependent cytotoxicity (CDC): PAT-SM6 recruits C1q to initiate the complement cascade, though this effect is secondary to apoptosis .
Non-contributory Mechanisms
Target Expression in Multiple Myeloma
| Parameter | PAT-SM6 Binding (%) | Sample Size (n) | Source |
|---|---|---|---|
| De novo MM patients | 87 | 11 | |
| Relapsed MM patients | 97 | 9 | |
| Healthy plasma cells | 0 | 4 |
PAT-SM6 showed 100% binding to CD138+ MM cells in flow cytometry and homogenous membrane staining in 92% of bone marrow biopsies (n=20) .
In Vitro Cytotoxicity
| Cell Line/Type | Apoptosis Induction | CDC Activation | ADCC Activation |
|---|---|---|---|
| INA-6 MM cells | Yes | Moderate | No |
| Primary MM cells | Yes | Moderate | No |
| Normal plasma cells | No | No | No |
Apoptosis occurred within 24–48 hours post-treatment, with caspase-3/7 activation confirmed .
Phase I Trials
Melanoma (ACTRN 12610000733077)
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Safety: No serious adverse events in 12 patients receiving up to 6 mg/kg .
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Efficacy: Reduced tumor volume in pre- and post-treatment biopsies .
Multiple Myeloma (NCT01727726)
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Design: 12 heavily pretreated relapsed/refractory MM patients received four intravenous doses (0.3–6 mg/kg) .
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Outcomes:
Advantages and Limitations
| Strength | Challenge |
|---|---|
| Tumor-specific targeting | Limited penetration in solid tumors |
| Synergy with proteasome inhibitors | No ADCC activity |
| Favorable safety profile in early trials | Requires combination therapies |
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
PAT-6/actopaxin plays a crucial role in regulating cell adhesion and cytoskeleton organization. It is a component of the integrin-containing attachment complex, essential for muscle development and maintenance. During embryonic development, PAT-6 is required for recruiting cpna-1, unc-89, and myofilaments to newly forming integrin attachments. These attachments consist of integrins pat-2/pat-3, pat-4, and unc-112. PAT-6 is also vital for repositioning these attachments to form the highly organized structure of dense body and M-line attachments characteristic of mature muscle cells.
Furthermore, during the formation of neuromuscular junctions in the larval stage, PAT-6 negatively regulates membrane protrusion from body wall muscles.
- PAT-6/actopaxin plays essential roles during the maturation of integrin-mediated muscle attachments in vivo. PMID: 12781130
