G47Δ (Delta) Oncolytic Virus: A Breakthrough Therapy for Glioblastoma from Prof. Todo in Japan

Great News for Glioblastoma

Today I came across these news (Ref.) coming from Japan, discussing a virotherapy that may represent a breakthrough therapy for brain cancers and possibly other cancers.

Oncolytic virus therapy is a very relevant approach to address cancer where viruses are converted into therapeutic agents as they are reprogrammed to treat diseases. Prof. T. Todo is one of those scientist who spent a major part of his life on studying and manipulating viruses in order to selectively target cancer. He did that first in US and latter back in Japan, by genetically processing herpes virus and as a result developing an advanced virus called G47Δ (Delta) that targets only cancer cells.

G47Δ was first developed by Prof T. Todo in 2001 and is a third-generation oncolytic virus (i.e. contains three mutations). Due to these mutations, the virus can replicate only in dividing cells, such as tumor cells.

The earlier, second generation oncolitic virus, was called G207  and it was the first oncolytic HSV-1 tested in a clinical trial in USA. Its high safety and potential antitumor activity were demonstrated in patients with glioma, both when administered alone and in combination with radiotherapy (Ref.).

During the past years, after his return to Japan, Prof Todo performed first a phase I–IIa clinical trial, and latter a phase II clinical trial in patients with recurrent glioblastoma. The latest results coming from this clinical trial will be presented on November 17, 2019 at the 5th Cancer Eradication Summit, under the title “The Forefront of Viral Therapy that has Begun to Move to Practical Use”. (Google translation from Japanese).

The great news presented at the summit and that I would like to share with you here is that the survival rate of 13 patients after 1 year has recorded an amazing number of 92.3%, compared with 15% for conventional drugs. A maximum of 6 intratumoral doses of the virus were given to the patients. Side effects were very limited, i.e. only 2 out of 16 people had fever.

More about G47Δ in clinical trials on Glioblastoma and other cancers

According to a paper published by Prof Todo and colleagues (Ref.) G47Δ was and it is currently tested on multiple cancers:

The first Phase I–IIa clinical trial of G47Δ was performed in patients with recurrent glioblastoma from 2009 to 2014 at The University of Tokyo. Its results demonstrated the safety of G47Δ when injected into the human brain (UMIN000002661).

The subsequent phase II investigator-initiated clinical trial started in 2015 at The University of Tokyo, to test the efficacy of G47Δ in patients with residual or recurrent glioblastoma (UMIN000015995). In the study, a dose of 1 × 109 PFU is injected stereotactically into the brain tumor twice within two weeks and every four weeks thereafter, a maximum six times.

Besides the clinical trials in glioblastoma, a single arm Phase I study in patients with castration-resistant prostate cancer was started at The University of Tokyo in 2013 (UMIN000010463). 3 × 108 PFU of G47Δ was administered into the prostate using a transrectal ultrasound-guided transperineal technique repeatedly (2–4 cycles) for nine patients (1–3). This study was completed in 2016, and its results demonstrated the safety of G47Δ when injected into the prostate.

Another study in patients with recurrent olfactory neuroblastoma (UMIN000011636) was started at The University of Tokyo in 2013. This trial is currently underway and is targeting a total of 10 patients.

In February 2016, G47Δ was designated as a ‘Sakigake’ breakthrough therapy drug by the Ministry of Health, Labour and Welfare of Japan.

In addition to the four clinical trials described above, a study of G47Δ for the treatment of malignant mesothelioma was just approved in March 2018 at The University of Tokyo.

Virotherapy in Germany

For those looking for a virotherapy treatment option in Germany, Dr. Arno Thaller seems to be the best option www.praxis-thaller.de I haven’t met him yet, but he was recommended to me by multiple patients as he seems to be the source of the most oncolytic viruses used at cancer clinics in Germany. One day, I intend to visit his clinic to learn more about the available treatment options.

References

Oncolytic virus therapy in Japan: progress in clinical trials and future perspectives https://www.ncbi.nlm.nih.gov/pubmed/30462296

Oncolytic virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming normal cells. T-VEC (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in 2015 and subsequently approved in Europe in 2016. Other oncolytic viruses using different parental viruses have also been tested in Phase III clinical trials and are ready for drug approval: Pexa-Vec (pexastimogene devacirepvec), an oncolytic vaccinia virus, CG0070, an oncolytic adenovirus, and REOLYSIN (pelareorep), an oncolytic reovirus. In Japan, as of May 2018, several oncolytic viruses have been developed, and some have already proceeded to clinical trials. In this review, we summarize clinical trials assessing oncolytic virus therapy that were conducted or are currently ongoing in Japan, specifically, T-VEC, the abovementioned oncolytic herpes simplex virus type 1, G47Δ, a third-generation oncolytic herpes simplex virus type 1, HF10, a naturally attenuated oncolytic herpes simplex virus type 1, Telomelysin, an oncolytic adenovirus, Surv.m-CRA, another oncolytic adenovirus, and Sendai virus particle. In the near future, oncolytic virus therapy may become an important and major treatment option for cancer in Japan.

Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors https://www.ncbi.nlm.nih.gov/pubmed/30524901

Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy.

Current status of clinical trials assessing oncolytic virus therapy for urological cancers https://www.ncbi.nlm.nih.gov/pubmed/28326624

Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEXGM-CSF ), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials. For example, a phase I trial of the third-generation oncolytic Herpes simplex virus type 1, G47Δ, in patients with prostate cancer was completed in 2016. We summarize the current status of clinical trials of oncolytic virus therapy in patients with the three major urological cancers: prostate, bladder and renal cell cancers. In addition to Herpes simplex virus type 1, adenoviruses, reoviruses, vaccinia virus, Sendai virus and Newcastle disease virus have also been used as parental viruses in these trials. We believe that oncolytic virus therapy is likely to become an important and major treatment option for urological cancers in the near future.

Oncolytic virus therapy: A new era of cancer treatment at dawn https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084676/

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T‐Vec (talimogene laherparepvec), a second‐generation oncolytic herpes simplex virus type 1 (HSV‐1) armed with GM‐CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T‐Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX‐594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM‐CSF‐expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild‐type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47∆, a third‐generation oncolytic HSV‐1, is ongoing in glioblastoma patients. G47∆ was recently designated as a “Sakigake” breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47∆ with priority reviews and a fast‐track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor‐specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.

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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23 thoughts on “G47Δ (Delta) Oncolytic Virus: A Breakthrough Therapy for Glioblastoma from Prof. Todo in Japan

    1. Hi Johan,

      I am not sure about that but according to the Japanese article Prof Todo states the following: “This was done with the guidance of PMDA, and it was proved that the side effects and other safety are good, so I would like to apply and approve it. I have been asking myself to deliver to you as soon as possible, so I would like to ask the government to support it so that it can be applied to all cancer types in the future.” So it seems that he is doing his best.

      In any case, given the fact that the toxicity in humans is now known and looks good, the regulation in countries like Germany allows to be applied in patients who do not have other treatment options left. So a patient that wants to use this virus has to now find a scientist that is willing to prepare it for him a doctor to administer. It can be the same person, and I think it should be possible.

      Kind regards,
      Daniel

  1. What’s equally amazing is that this story isn’t getting much traction yet, at least not outside of Japan. This news has been out in Japan for about 5 weeks and it seems you are the first to report on it, Daniel! If Mr. Donald Trump sneezes I read about it in Chile the next hour, and here we have 12 out of 13 patients with recurrent GBM who are alive after a year, and the side effect of the treatment was fever(!), and only in 2 patients!? I know it’s still early days, but this type of results in one of the deadliest cancers, even if it went downhill from here it would still be amazing, precious time is gained with great quality of life.

    1. I agree Johan, this is very exciting research! I was very excited to see that they are working on other cancers, and prostate cancer was one of them! Great detective work, Daniel.

      1. Hi Carol, I have a feeling this is going to change things, you don’t get this kind of result with glioblastoma if it wasn’t something that hits cancer at its core. I know there are lots of different cancer types but if you can tame the most aggressive one, the fastest-growing cancer, then I believe we can expect many other types of cancers to react in a similar way. I’m very happy for you and so many others who are doing EVERYTHING they can to delay cancer progression and determined to beat it. With news like this now more than ever it´s worth trying to slow down cancer with what is currently available, and pray this new treatment is made available to the public asap.

  2. Hi Daniel,

    I read through this article and followed the links. The FDA approved a virus for use in advanced melanoma patients and I saw there was a trial for CRPC – which we are very interested in the results but didn’t really find any specifics. Doesn’t look like an option for us right now with rising PSA, will need to use everything else available. I found this paper on the Current status of clinical trials assessing oncolytic virus therapy forurological cancers, dated 2017 which might be helpful:

    https://onlinelibrary.wiley.com/doi/pdf/10.1111/iju.13325

    Carol

    1. Hi Carol,

      Indeed, this seems not to be available. However, you can always contact the German doctor expert in viruses that I mentioned at the end of the article and see if he can get it for you, or something similar. It’s always good to be informed about whats available. But in any case, I would first consider the prostate cancer treatment options Shanti and I discussed on this website.

      Kind regards,
      Daniel

  3. Hi Daniel and all,
    Hope you are all doing well!

    Dear @Daniel, so many thanks!
    Indeed great & unique (hard to find) news from Japan, which give more hope to have a whole and through solution in the future.

    Dear all,
    I want to share my thoughts with you –
    I am only about 7 months in this new era of cancer but feel I already understood some of the main limitations of standard cancer treatments and the too slow introducment of new promising therapies.

    Even when it comes to such positive info from Japan, I assume that most of the professional and even patients communities in the world will not hear about it, due to lengual differnces but mainly due to the fact of the western countries and especially the US traditionally dominating studies, clinical trials and standartization of new treatments (FDA).
    I am not saying this negatively (with lot of respect to the historical and current contribution) but in some cases it is a blocker for considering and accepting other therapies.

    Another blocker is the size of the trials which is directly influenced by the funding.
    In cases where there is a big pharma supporting the trial it is likely to be bigger, thus when successful it has higher chances to become SOC (Standard Of Care).

    So, what can WE do to help?
    Each one of us is a member in other social networks and communities (related and unrelated to cancer). Each one of us has a doctor that is usually unaware of this info.

    * SPREAD THE INFO WHEN CONSIDERED VALUABLE and
    MAKE MORE PEOPLE BE AWARE OF IT!
    * MAKE YOUR DOCTOR BE AWARE OF IT and ASK HIM TO CHECK IT!

    It is not easy but I truly believe we also have to help make the change!

    Best wishes to all!!!
    Nissim

    1. Hi Nissim,

      I very much agree. It’s very nice that you are thinking about this.

      Indeed it is very important to spread the knowledge and create awareness. What I learned is that it is best to focus on patients as most of the doctors are too busy and in many cases eve if they are aware of new treatments they may not be allowed to implement or they do not have a protocol for their implementation.

      In addition to that, I think we, the society, need to focus on the following in order to get to a better shape of the medical system when it comes to oncology:
      – push for new regulations around the world that allow and stimulates doctors to do more for their patients
      – create organisations that bridge the academic findings with clinical space by defining protocols of administration for the most relevant findings, and train the medical doctors so that they know when and how to implement these
      – lower the threshold for new drug approval (today it takes 10 years, 1 billion USD and 98% failure to get a drug to market)
      – allow patients to chose the type of treatment they are going to have, i.e. patient can jump to e.g. second or third line if he wants

      I would have so much more to say here, but I stop for now 🙂

      Kind regards,
      Daniel

      1. Fast Track, a new FDA program, has cut the time down significantly where these drugs can be approved within a couple years for diseases that claim an unusually high number of deaths where prognosis is very low, and the promise for the drug appears to be very high. I would think that this should qualify, but if I know anything about the FDA, is that something like that is a pay to play and it’s a price tag (and privilege) only available to big pharma, and probably only for things where the payback is likely to be high. What is really needed is not just a FastTrack, but a provisional exemption, which would be much cheaper, where the drug is approved on a provisional basis where these same criteria are met. That simply means it will be treated as an approved drug but additional testing is required, most likely reserved for stage 4 refractory cancers (which a lot of Glioblastoma are).

        1. You are right lullabyman. The points in my comment above are related to the general situation around the world. When zooming in at the country level, they may be different. Fast Track in US allows indeed approval of some drugs on a time frame shorter than 10 years now. Also, Germany allows oncologist to do more for their patients compared to most countries, which I very much like and appreciate. But, while some countries are more or less ahead compared to other, it’s clear that overall much more has to be done along all the directions indicated above in order for the patients to have major improvements in terms of outcome.

  4. Great contribution Daniel!
    Unfortunately I doubt we can benefit and the private cost is unassumable …
    I could fight the option of compassionate use but I would have to spend all my energy fighting in several hospitals.

    Kind regards

    1. Hi Manuel,

      I don’t have time now but I may be able to give a call in a week or so to dr. Thaller mentioned in the post. He may have this onco virus and it may be accessible in terms of cost. It’s good to at least know if people can have access to it.

      Kind regards,
      Daniel

      1. Thank you very much Daniel!
        I think it can be effective, although logically I am worried about the high price …. I can study how to obtain it … you know that I am good at eating my head! Hahaha

        kind regards

  5. Hello,
    I came aware of this post via a patient.
    For sure, oncolytic virus will become an important part in the treatment of cancer. They have a dual role: they are directly oncolytic, and break down tumor cells, even cancer stem cells. They however can also induce immunogenic cell death, thereby stimulating the immune system so that the effect of the virus is strengthened and prolonged via the immune system of the patient.
    All these research lines are now very important and very exciting.
    If one mentions “Virotherapy in Germany”, one should also mention the IOZK where Newcastle Disease Virus is available as a GMP (Good Manufacturing Practice) product, approved for use in the maturation of patient-specific anticancer vaccines that are approved medicinal products for use in human. The vaccine is called IO-VAC.

    1. Dear Stefaan,

      Thank you for your comment. I am aware of the existence of IOZK, and from time to time I am in contact with your patients, but I to not have a clear view on the treatment options at your clinic and the related results. Given that I live in the Netherlands, I would be glad to meet you and discuss in more details these points. In addition, on this website, I intend to create a new section where experts in various oncology fields that I find relevant, will be invited from time to time to share their opinion on cancer treatments related to their field of expertise. The information will be informal, unbiased and actionable. Since I understand you are such an expert, a former University professor with both PhD and MD degrees and working for long time in the field of Virotherapy (a field that I find very relevant), I would like to invite you to be one of the first to share your view on this website. If you find this a good idea, please let me know and I will be glad to continue the discussion via e-mail.

      Kind regards,
      Daniel

    1. Hi Manuel,

      I am in contact with Dr. Van Gool and will soon arrange a meeting at IOZK in Koln. It’s about 2h driving from my home. If you or others have any points you like to address, please let me know.

      Kind regards,
      Daniel

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