Hi,
again thanks for a great book and apologies for sending you so many questions. I have two questions that I hope you can help with:
1. Can IL-2 be a good substitute for Coley's toxin?
As I am sure you are aware, there is quite a bit of research on the use of IL-2 in immunotherapy. A recent article from a group at MIT also included IL-2 (a long half life version) in an immunotherapy cocktail that was tested preclinically (with very promising results). Here is their paper:
Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses.
https://www.ncbi.nlm.nih.gov/pubmed/27775706
Furthermore, there is also a doctor in Vienna, Austria, who has a IL-2 treatment protocol that he offers patients. A case study based on this protocol was published at ASCO this year:
http://meetinglibrary.asco.org/content/166013-176
Can I ask what you think of IL-2? Can it be a potential substitute for Coley's toxin? Or are there reasons to believe Coley's toxin is preferable?
2. Do you know if Coley's toxin is available from any reliable sources today?
Kind regards,
Lars
Hi Lars,
I have been following your blog and your wife's story for a while. I am also very interested in Coley's toxins. I understand there is no reliable source to get it. I am thinking out of desperation to try to make it by myself.
IL-2 study looks promising. I wonder what was the long term outcome for the patients in this study. Do you mind to share the name of the Doctor in Vienna who follows this protocol?
You probably know that there is a vaccine in Cuba for lung cancer, Cimavax.
Thank you for any information. I wish your family well.
Tanya
Hi Tanya,
the doctor in Vienna is Dr Ralf Kleef. Here is his website: http://www.dr-kleef.at/en.
I have also heard about the Cimavax vaccine. I doubt it would do a lot on its own, but it could be good in combination with maybe a tyrosine kinase inhibitor (such as e.g. erlotinib) and maybe it could also be good in combination with other immunotherapy.
Best,
Lars
Hi Lars,
We did look into IL-2. IL-2 has a long history in immunotherapy. Our impression is that the benefits have been somewhat limited, and that checkpoint inhibitors are generally significantly more effective.
IL-2 is not a replacement for Coley's Toxins. Coley's has a non-specific mode of action and it up/down-regulates many different cytokines/chemokines, not just IL-2. I don't think anyone has fully characterized the complete extent of its effects.
We are not aware of any reputable source of Coley's Toxins beyond MBVax. Unfortunately, as far as we know, MBVax is no longer manufacturing. A few months ago we did hear of a clinic in Japan that was administering a version of Coley's but have no idea as to the reliability, efficacy or safety.
It is amazing to witness the vast array of immunotherapy offerings that have mushroomed in the recent few years.
Many vaccines can be combined with checkpoint inhibitors for maximum effect (as described in our book). You may also want to take a look at heat shock protein vaccines (such as by Heat Biologics and other such companies). This combination approach is what we would recommend. Indeed, this seems to be the direction that many companies have chosen in the recent years.
Also described in our book, is the importance of local application to mimic Dr. Coley's direct injections into tumors. We describe injection of CpG (you asked for something similar to Coley's, this would be much closer than IL-2). You could seek to combine that with anti-PD-1 / anti-CTLA-4, on top of a vaccine.
Best
Edward & Rene
Hi Rene and Edward,
thanks a lot for this. I have only barely heard about CpG and will try to read up on it.
Heath shock proteins: I have heard a bit about these. Do you know if anyone are available today? Or are they all still in trials? Apologies if this is a stupid question revealing I know very little about this...
I read with great interest the chapter on intratumoral injection. A few weeks ago, I spoke with a very well reputed professor here in Norway about my wife (who has stage IV lung cancer) and she suggested trying to do an intratumoral injection in the lung tumor to help boost the immune response. Hence we are looking into this, and reading your book gave further motivation to pursue this approach. One challenge, however, is that with lung tumors it is not so easy to do intratumoral injection (it is actually quite difficult and a little bit risky). So it will not be possible to do it very frequently (like you did with Coley's toxin). I guess we will only be able to make one intratumoral injection, or perhaps a few over the space of some time. We will see what we can manage to organize.
Best,
Lars
Hello Lars,
Yes, intratumoral injections in the lung would be trickier. Working with a skilled interventional radiologist would be advisable (there are those skilled in cryoablation, RFA etc). Also, choosing a tumor that's in a "safer" location may be considered (since the goal may not be direct ablation of a problematic lung tumor, rather just to activate a tumor-specific response).
It definitely takes thought, effort and work. But looking back, the lung cryoablations were a piece of cake compared to lung surgery. We would think that an intratumoral lung tumor injection should approximate a lung cryo in terms of morbidity (pain, swelling etc). If so, it, too, could potentially be just as easily tolerated as lung cryo (just thinking out loud).
Heat Shock Proteins: I know there are trials. Not sure if any have been approved and available off-label yet. Sorry. In any case, it would be just one component of an immunotherapy approach we would adopt.
Best,
Edward and Rene
Intratumoral injection in a lung tumor is definitely not something we would want to do ourselves :) I admire the way you dared to do it in the jaw. However, the lung is probably a step too far.
We are in contact with an interventional radiologist who may be willing to do an intratumoral injection. But not sure if we can convince him. There are, unfortunately, only a very few people who do cryoablation in lung. And in most countries they would be too scared to deviate from the "normal" cryoablation and instead do an intratumoral injection. But we have found one in Germany who may be willing. But not certain yet. Do you think Dr Littrup would be open to do this?
Again, thanks a lot for your kind help and advice on this.
Lars
In the US, it is extremely difficult to get something like this outside the context of a clinical trial. I believe MD Anderson was planning on (maybe already is) running a clinical trial involving CpG injection or maybe some other Toll Like Receptor agonist.
You might consider getting the injection as part of a clinical trial if you can't find someone to do this off-label.
A relevant publication:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489745/
Ok, thanks for this. We will continue doing research on this and see what we can manage to implement.
Best,
Lars
Hi Lars
I have been following yours and your wife story here. I am battling stage 4 synovial sarcoma in a lung and I was wondering if you have found anyone in Germany who agreed to do the cryoblation there. If you did would you be so kind to let me know where I can find him please?
Urszula
Hi Urszula,
Professor Thomas Vogl may be able to help: https://en.wikipedia.org/wiki/Thomas_Vogl. He can be reached at t.vogl@em.uni-frankfurt.de. And his secretary can be reached at Sigrid.Potapczuk@kgu.de. Note that I am not certain if Prof Vogl does cryoablation or if he only focuses on other forms of ablation.
In London I have heard good things about Dr Alice Gillams (http://www.thelondonclinic.co.uk/consultants/dr-alice-gillams). She should be good with cryoablation.
Finally, there is also a professor in London called Edward Leen (http://www.theprincessgracehospital.com/specialist-search/professor-edwa...). He is good with NanoKnife (irreversible electroporation) and also other forms of ablation. He can be reached at edward.leen@csc.mrc.ac.uk.
I hope this helps.
Lars
Thank you so much Lars!
I will try first 2 people in London.
Urszula
Hello Rene and Edward,
Thanks to your inspirational story, we have been on our own journey curing cancer with immunotherapy. My boyfriend was diagnosed with synovial sarcoma on his right hand 1.5 years ago and had the tumor removed with clear margins. Everything was great until March 2017 when we found out he had nodules in his lungs. We found Rene and Eddy's book a few days after the diagnosis, and after consulting our doctors, who told us that the chances of curing him with chemotherapy were close to zero, we decided to put all our efforts into immunotherapy.
We recently travelled to Tijuana and were able to get Coley's toxins. We are doing more research before starting the injections, and we would like to know more about your experience.
I read in your blog (http://cancerwife.com/content/were-back-alive-and-kicking) that after 2 months of tumor shrinkage with Coley's toxins monotherapy there was reversal regrowth. I couldn't find your theories as to why this happened and was wondering if you could elaborate. Also, do you think too frequent injections of Coley's toxins caused too much immunostimulation and thus cachexia? Or do you have other theories as to why Rene experienced cachexia? It would help us greatly in planning our treatment course.
Thank you so much for your time and kindness.
Your story gives us hope and strength every day,
DY and YS
DY and YS,
We moved your question to a different thread and answered it there: http://www.curingcancerbook.com/synovial-sarcoma-questions-regarding-col...