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

Dear Friends,

I just came across a recently published paper by scientists and MDs in oncology that deserves to be addressed in a post on this Blog. The scientific results come from MD Anderson Cancer Center & University of Alabama at Birmingham in USA, as well as Zhejiang University School of Medicine & Medical School of Southeast University in China. The list of authors is very long, the paper where these research findings have been published is a very good one, i.e. Cancer Immunology Research. All these aspects add to the credibility and relevance of the present results.

Before addressing the subject of the paper mentioned above, I would like to remind you that if you like the type of content presented on this website, Cancer Treatments Research, and if you like to see this moving forward, please support us. The most convenient way for people to support our continuity is to buy (some of) their supplement at MCS Formulas. This will insure the continuity of Cancer Treatments Research website, as well as many projects that MCS Formulas supports and will support as a social enterprise, donating 50% of its profits to projects to extend and improve the lives of cancer patients. Thank you in advance for your help!

Recently, on 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/product/visudyne-pulver-f-infusionsloesung.30249.html

Disclaimer

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?page_id=1794

 

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4 thoughts on “A Lower Cost Alternative to (anti PD1/PDL1) Immunotherapy?

  1. Hi D, thanks again for the valuable work and information.
    It seems like I no longer get email notifications on new articles, are you aware if anyone else has this issue? Sorry about the off-topic question

    1. Hi Pouya,

      Nice to hear from you and thank you for your msg. In the past, I could use a free plugin to send the notifications. But now, because there are a lot of registered users to whom the notification will be sent, I need to pay a fee of 60USD/month only for this functionality, next to all the other (higher) costs related to the web-hosting and maintenance. However, this 60USD is exactly the amount of all donations I received during the past month. Therefore, the cost to maintain this website goes beyond the amount of donations I receive now – so I nee to manage the costs very carefully. In order to do this, I will activate the subscription for notifications and pay 60USD only when I think the post I wrote really needs to get to people, and than I switch that off.

      I hope you are well Pouya and things are going well on your side! I ‘ve seen on your FB page you made very nice drawing! Congratulations for that!

      Kind regards,
      Daniel

  2. Hi Daniel,
    thank you very much for sharing information on cheaper alternatives to immunotherapy.

    Also using PD1/PDL1 inhibitors in lower doses than normally prescribed can be an effective strategy.
    Below are some articles that confirm that low dose immunotherapy is still effective. Nivolumab is the
    cheapest of this class of drugs and for my mum we chose to self-finance low-dose Nivolumab.
    Another hope (for Asian patients) could be a new generic of Nivolumab – Nivolunix – launched last month
    by Beacon in Bangladesh – hopefully the price will be much lower than the price of Opdivo (link below)

    https://www.ncbi.nlm.nih.gov/pubmed/30094065
    Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity

    Immune Checkpoint Inhibitor Dosing: Can We Go Lower Without Compromising Clinical Efficacy?
    https://ascopubs.org/doi/10.1200/JGO.19.00142

    https://www.beaconpharma.com.bd/beacon-medicare-limited-launches-nivolunix/

    1. Hi Michal,

      I totally agree that low dose may work! Back in 2015 we were doing low dose Nivolumab at 1mg/kg one time per month and the claim of the private clinics using it in Germany was that even lower dose (o.5mg/kg) may do the job. Unfortunately, even that low dose we used triggered tumour progression (which we stoped with Diflunisal) and side effects. So it’s clear that even such low dose is doing something. At that time we paid about 1000 to 1500 euro for the 1mg/kg we used.

      Thank you for sharing the info!

      Kind regards,
      Daniel

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