Polatuzumab Vedotin

(RG7596)

Polatuzumab vedotin image: an investigational anti-CD79b ADC designed to bind to the CD79b portion of the B-cell receptor
Breast
  • Phase
  • I
  • II
  • III
Gastrointestinal
  • Phase
  • I
  • II
  • III
Genitourinary
  • Phase
  • I
  • II
  • III
Gynecologic
  • Phase
  • I
  • II
  • III
Hematologic
  • Phase
  • I
  • II
  • III
Lung
  • Phase
  • I
  • II
  • III
Melanoma
  • Phase
  • I
  • II
  • III
Solid Tumor
  • Phase
  • I
  • II
  • III

This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.

Polatuzumab vedotin, an investigational anti-CD79b antibody-drug conjugate (ADC)

Polatuzumab vedotin, an investigational anti-CD79b ADC, is currently in clinical development based on its potential to selectively bind to CD79b expressed on malignant B cells.1-3 CD79b is a transmembrane protein expressed on the surface of B cells as part of the B-cell receptor complex.2

Polatuzumab vedotin is comprised of a CD79b-specific monoclonal antibody conjugated to a cytotoxin, via a stable linker. These 3 components together are designed to deliver highly potent cytotoxins directly to tumor cells, which then internalize and release the cytotoxin intracellularly.1,4 In preclinical in vitro models, data have shown that an anti-CD79b ADC effectively and selectively eliminated cells expressing CD79b.2 Polatuzumab vedotin continues to be investigated in ongoing clinical studies.

Polatuzumab vedotin image: an investigational anti-CD79b ADC currently being studied for its potential to selectively bind to CD79b expressed on malignant B cells

1 Polatuzumab vedotin is an investigational anti-CD79b ADC currently being studied for its potential to selectively bind to CD79b expressed on malignant B cells.1-3 Polatuzumab vedotin is designed to bind to the CD79b portion of the B-cell receptor, triggering internalization of the receptor complex by the cell.1-3,5,6

Polatuzumab vedotin image: binding to the CD79b portion of the B-cell receptor triggers internalization of the receptor complex and release of cytotoxic monomethyl auristatin E

 

Once internalized, the stable linker of polatuzumab vedotin is cleaved, releasing cytotoxic monomethyl auristatin E (MMAE) that binds to microtubules.6,7

Polatuzumab vedotin image: preclinical data have demonstrated cytotoxic monomethyl auristatin E triggers cell apoptosis in vitro

 

3 Preclinical data have shown that MMAE inhibits microtubule polymerization, disrupts cell division, and triggers apoptosis in vitro.5,7 Polatuzumab vedotin continues to be investigated in ongoing clinical studies.

References

  1. Palanca-Wessels MC, Czuczman M, Salles G, et al. Lancet Oncol. 2015;16(6):704-715. PMID: 25925619
  2. Polson AG, Yu SF, Elkins K, et al. Blood. 2007;110(2):616-623. PMID: 17374736
  3. Dornan D, Bennett F, Chen Y, et al. Blood. 2009;114(13):2721-2729. PMID: 19633198
  4. Peters C, Brown S. Biosci Rep. 2015;35(4). pii: e00225. PMID: 26182432
  5. Beck A, Lambert J, Sun M, Lin K. MAbs. 2012;4(6):637-647. PMID: 22909934
  6. Schrama D, Reisfeld RA, Becker JC. Nat Rev Drug Discov. 2006;5(2):147-159. PMID: 16424916
  7. Francisco JA, Cerveny CG, Meyer DL, et al. Blood. 2003;102(4):1458-1465. PMID: 12714494