CXE4 Antibody

Introduction to CXCR4 Antibodies

CXCR4 (CD184) binds its ligand CXCL12 (SDF-1) to regulate cell migration, hematopoiesis, and tumor microenvironment interactions . Antibodies against CXCR4 block these interactions, offering therapeutic potential in oncology and immunology. Over 1,900 studies describe their use in flow cytometry, immunohistochemistry (IHC), and functional assays .

Mechanisms of Action

CXCR4 antibodies exhibit dual mechanisms:

• Receptor Blockade: Inhibit CXCL12 binding, disrupting chemotaxis and signaling (e.g., 2B11 monoclonal antibody) .

• Fc-Effector Functions: IgG1 antibodies like PF-06747143 induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) .

For example, PF-06747143 reduced tumor burden in non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML) models by mobilizing malignant cells from protective bone marrow niches .

Therapeutic Trials

• Ulocuplumab (BMS-936564): A phase Ib/II trial in relapsed/refractory multiple myeloma showed a 55.2% response rate when combined with lenalidomide/dexamethasone. Neutropenia (43.3%) was the most common adverse event .

• MDX-1338: In non-small cell lung cancer (NSCLC) xenografts, 89Zr-labeled MDX-1338 identified high-CXCR4 tumors, correlating with therapeutic efficacy (60% tumor weight reduction) .

Diagnostic Imaging

• 89Zr-CXCR4-mAb: PET imaging detected CXCR4 overexpression in NSCLC and triple-negative breast cancer (TNBC), guiding therapy selection .

Preclinical Studies

Functional Comparisons

• 2B11 (PE-conjugated): Binds CXCR4’s N-terminus, causing receptor internalization without blocking SDF1α .

• Rabbit Polyclonal Antibodies: Used in Western blot (70 kDa band) and IHC .

Challenges and Future Directions

• Tumor Heterogeneity: CXCR4 expression varies across malignancies, requiring biomarker-driven patient stratification .

• Combination Therapies: Synergy with chemotherapy (e.g., gemcitabine) is under investigation to overcome resistance .