PD-L1 Inhibition + VEGF Inhibition

VEGF can suppress the antitumor immune response

Vascular endothelial growth factor (VEGF) promotes vascularization, which is often exploited by tumors to stimulate angiogenesis needed for tumor growth and metastasis.1

VEGF also has the ability to disrupt a key step in the cancer immunity cycle: T-cell infiltration into the tumor.2,3

VEGF inhibition may help T cells infiltrate the tumor microenvironment

Targeting VEGF may help restore part of the cancer immunity cycle by increasing T-cell infiltration into the tumor microenvironment.3-5

  • VEGF pathway inhibition may lead to increased expression of cell adhesion molecules on endothelial cells, increasing intratumoral T cells to create an immune inflamed tumor microenvironment
VEGF pathway inhibition leading to T-cell infiltration

Targeting VEGF and PD-L1 may have a synergistic effect on restoring antitumor activity

Inhibition of the VEGF and PD-L1 pathways is a rational combination with the potential for enhancing immune responses. The effects of VEGF inhibition can create an inflamed tumor microenvironment that is optimized for PD-L1 inhibition.2,4,6

Genentech is actively researching the combination of VEGF inhibition and PD-L1 inhibition in various tumor types.7,8

VEGF inhibition + PD-L1 inhibition restores cancer immunity

PD-L1=programmed death-ligand 1.

*Tumor cell killing by CD8+ T cells.

References

  1. Hicklin DJ, Ellis LM. J Clin Oncol. 2005;23:1011-1027. PMID: 15585754
  2. Kim JM, Chen DS. Ann Oncol. 2016;27:1492-1504. PMID: 27207108
  3. Terme M, Colussi O, Marcheteau E, Tanchot C, Tartour E, Taieb J. Clin Dev Immunol. 2012;2012:492920. PMID: 23320019
  4. Hughes PE, Caenepeel S, Wu LC. Trends Immunol. 2016;37:462-476. PMID: 27216414
  5. Wallin JJ, Bendell JC, Funke R, et al. Nat Commun. 2016;7:12624. PMID: 27571927
  6. Chen DS, Mellman I. Nature. 2017;541:321-330. PMID: 28102259
  7. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02420821. Accessed November 1, 2017.
  8. US National Institutes of Health. ClinicalTrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT02366143. Accessed November 1, 2017.
  9. Chen DS, Mellman I. Immunity. 2013;39:1-10. PMID: 23890059