Week 60: Some very preliminary results on vaccine efficacy

Written by Lars Haakon Soraas
16
Oct

Week 60 in the war on cancer has passed. Here are the highlights:

  • Dyanne has been in quite good shape. A bit tired and quite a bit of rash on legs and arms, which most likely are side effect of the immunotherapy treatment she is getting. Cough seems to have gone.
  • She was in Frankfurt this week and got another injection of the personalized peptide vaccine and also a small dose of nivolumab.
  • They measured again, using ultrasound, the lymph node above her right collar bone. The lymph node has increased a little bit in size, but the doctor is not worried, as the lymph node previously shrank a bit. The doctor says that if it was cancer, it would not have shrunk. We will, in any case, continue to monitor the lymph node.
  • While in Frankfurt, she also learned the first, very preliminary, test results they have done to try to understand whether the vaccine is working or not. More on this below.
  • We got the results of some analysis that a US-Indian company called CellWorks has done. In short, they have done computer simulation (“in silico simulation”) using the mutation data that was found from the exome sequencing which was done as part of the vaccine development. Based on their simulations, they have suggested a treatment that potentially can be effective. The methodology is, rest assured, not yet proven in trials. However, given what we know about tumor heterogeneity, I think it will be this kind of 100% personalized approaches that one day will help humanity conquer cancer. Personalized vaccines, like the one Dyanne is getting in Germany, is another approach that takes the issue of tumor heterogeneity seriously.

Vaccine status

Many people ask us how the vaccine is going and if it is working. The fact is that we will never know with certainty whether the vaccine is working or not. We may get some indications, but certainty we will never get. The best “proof” of the vaccine working is if Dyanne, when she is 92 years old, dies of a lightening. However, even then we will not know for sure whether it was the vaccine or some of the other treatment she has is getting that held cancer at bay. Even if this may sound a bit frustrating, it really is not. As long as Dyanne is in good health and is thriving, we don’t really care whether it is the high tech vaccine, the low tech fish oil, the abstract meditation or the expensive osimertinib that is working. As long as something works, we are happy 🙂

As for the, very preliminary, results of the vaccine, first some background and caveats:

  • They have tested whether any of the peptides that was in the first batch of peptides Dyanne got (5 short and 4 long peptides) produce any immune response when they mix the peptides with her own immune cells (separated from a blood sample). We should mention that Dyanne is now also getting a second batch of peptides consisting of two short and two long peptides that were added in the beginning of August. They have not yet started testing if these are producing an immune response.
  • A negative result does not necessarily mean that the vaccine is not working. It may just need a bit more time to work.
  • A positive result does not necessarily mean that the vaccine is working. Based on modelling, it is hoped that the peptides are expressed on tumor cells, but there is no guarantee for this. And even if they are, it is not sure that any response observed in vitro will translate to immune cells attacking tumor cells in the body. And even if they should do this, one cannot know if they do this with enough force and persistence to have a clinical impact.
  • I should also mention that the results are very preliminary and that they are doing further testing to try to verify what they have found so far.

With all these caveats, here are the, very preliminary, results:

  • The testing reveals that there is a quite clear CD4 response. This means that there is an immune response, and they think this is due to one of the peptides.
  • They have tried to investigate which peptide it is that is giving the immune results. They think they know which one it is, but are not certain.
  • They have checked if there was a CD4 immune response prior to the vaccine against this suspected peptide and they see that there was a bit of a response. However, it seems much stronger now, indicating that the vaccine (and/or the nivolumab and ipilimumab) is having an effect.
  • As for the magnitude of the response, they say it is a bit difficult to evaluate, but it seems to be medium, i.e. not very strong, but not very weak either.

We take this as positive news, even if we should be cautious in not overinterpreting these preliminary results. We eagerly await results from the further testing that the team in Frankfurt will be doing. And we also look forward to discussing with them if there are things that can be done to further potentiate the vaccine to try to make the immune system also recognize some of the other peptides (or even new ones that maybe can be added).

The “thank you section” I used to have at the end of these posts have been forgotten for a while. Not because there hasn’t been a lot of people to thank (there is), but because I have been lazy. Anyway, I today want to say thank you to an unnamed pathologist at UllevĂĄl hospital (we, and he, know who he is). When Dyanne did a CT guided biopsy from the lung tumor in August last year, he oversaw the procedure and made sure that a good amount of tissue was extracted. This tissue has been essential for both the personalized peptide vaccine, the CellWorks simulation mentioned above and also several other things. Captured tumor cells have become very very important in the war against cancer. And this one patologist helped us get a lot of them. Thank you!

dyanne-at-sognsvann

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