A Lower Cost Alternative to (anti PD1/PDL1) Immunotherapy?

In July 2020, the following paper has been published in Cancer Immunology Research journal:

Verteporfin Inhibits PD-L1 through Autophagy and the STAT1–IRF1–TRIM28 Signaling Axis, Exerting Antitumor Efficacy https://cancerimmunolres.aacrjournals.org/content/8/7/952.

With this the authors demonstrate that a drug called Verteporfin, an FDA approved drug (Ref.), inhibits PD-L1 expression within the tumor microenvironment – this in turn is associated with enhanced T-lymphocyte infiltration.

Verteporfin is an ophthalmological drug used as a photosensitizer for photodynamic therapy to address the abnormal blood vessels in the eye associated with conditions such as retinopathy.

Previous studies, have demonostrated that Verteporfin acts against multiple types of cancer due to several important mechanisms:

• First, it targets Yes-associated protein 1 (YAP1). This protein is playing an important role in the Hippo signaling pathway (Ref.1, Ref.2). I actually discussed this subject on this website many years ago here https://www.cancertreatmentsresearch.com/hippo/
• Second, Verteporfin has been shown to posses autophagy inhibition property, inhibiting autophagy in the early phase of the autophagosome formation (Ref.)

However, the activity of Verteporfin against PD-L1 expression was not known and is a novel finding.

In this recent study, the authors indicate two unique mechanisms of action of Verteporfin on PD-L1 expression:

• an autophagy-dependent mechanism leading to the loss of PD-L1
  • verteporfin induced autophagy-mediated degradation of the Golgi apparatus, which was likely a consequence of verteporfin-induced organelle damage –  there is a role for the oligomeric Golgi complex in regulating PD-L1 expression as a quality control mechanism
  • Chloroquine treatment abrogated verteporfin-induced loss of PD-L1
• verteporfin inhibited IRF1-dependent PD-L1 transcription
  • verteporfin blocked the IFN–IRF1–PD-L1 axis without collateral suppression of CIITA-dependent tumor immunogenicity

The authors also found that PARP inhibitors induced PD-L1 expression, and that was suppressed by Verteporfin. As a results they proposed that Verteporfin could be a great addition to PARP inhibitors. PARP inhibitors (Ref.) are a group of relatively recent drugs approved to tread e.g. ovarian, breast and prostate cancers.

In conclusion, Verteporfin could be a good alternative for those who cannot afford the very expensive anti-PD1/PDL1 immunotherapy but would still like to try this treatment avenue. In addition to the anti- PDL1 activity of Verteporfin, this also comes with other anti cancer actions such as Yes-associated protein 1 (YAP1) inhibition and autophagy inhibition. This, in my view makes Verteporfin very attractive as a potential anti-cancer treatment.

Indeed, the authors of the paper state the following: “Given the patient safety profile and relative low cost ($1700 per injection, wholesale), verteporfin could be considered as an alternative approach to PD-L1 blockade.” (Ref.).

The brand name of Verteporfin is Visudyne and here is an example of a pharmacy in Germany that has this drug available with prescription: https://www.apotheke4you.de/visudyne-pulver-f-infusionsloesung-00869382.

Source: https://www.cancertreatmentsresearch.com/a-low-cost-alternative-to-anti-pd1-pdl1-immunotherapy/