Tuesday, October 28, 2008

Activated t-cells - really?!?

Good morning. I guess you are probably wondering where I have been. Would it surprise you if I told you I was still without internet access from charter? Am I being emotional here? Isn’t this a bit ridiculous?

Well, just because I have not had internet access, it does not mean that exciting things have not taken place. Over the last few days we had a great golf tournament and even received report cards for the kiddos. It has been an exciting time. I will have to remember to tell you about them. However, right now, I just can’t get something off of my mind. I received a rather interesting email from Dr. Chrystal Louis regarding Sydney’s blood that we sent down to Houston. It has me in quandary. I have included the pertinent information from her email below. Here we go:

As you may know, part of the follow-up samples that we obtain from Sydney (and each patient) allows us to look for evidence of the cells that we infused. The activated T cells and EBV-CTLs were each transduced with a slightly different form of the GD2 receptor. We look for copies of each transgene, by PCR, in every follow-up sample. Sydney’s latest sample showed elevated copies of one of the transgenes. So what does this mean???

1) Was Sydney sick at the time of the blood collection? If she was, this could be a “viral” reactivation of GD2+ cells.
2) What was the result of her MIBG scan? Could this be secondary to a low level of disease and we happened to collect her at a time when she had a large number of cells in the peripheral blood?
3) Is this a false positive? Our lab has repeated the testing and does not think so, but they have requested an additional sample to confirm the results.

If we are able to confirm them, it would help to prove that T cells transduced with a GD2 chimeric antigen receptor are able to survive long-term after infusion. However, I appreciate that it requires an additional blood draw for Sydney. After much discussion, we felt that obtaining confirmation of the results was important enough to request an additional sample.

Scary? Well, yes, kind of. Given the fact that she was not sick at the time of the infusion and that their lab does not feel that this is a false positive I don’t think I like the other option. In fact, I don’t really know if I necessarily agree with her conclusions. In my novice view I would not expect the virus to be activated by a low level of disease. I know it sounds counterintuitive but it was the EBV (Epstein Barr Virus) that was expected to keep reactivating the cells. I do not believe that was the purpose of the antibody. The antibody was just the magnet to the neuroblastoma. In my understanding I never would have expected them to activate the GD2+ cells. However, that is less of a known fact and more of theoretical hypothesis. Bottom-line, I would have expected EBV to be the culprit.

Regardless, this is very interesting. From a scientific point of view, it could mean a tremendous amount. I have to admit that this is at least a little revolutionary. However, there is far less known that there is that is known about this vaccine and it’s apparent effects inside Sydney than there is that is known. I don’t believe that the 3 theories provided by Dr. Louis are the only possibilities. There are more.

So, for me, the question becomes – “What do we do now?” I am less concerned about the blood draw. That is a necessary evil for Sydney. As much as I hate putting her through another blood draw given her finicky veins, I think this is very important to know. I also wonder whether it may be worthwhile to move up her bone marrow aspiration to do at the same time. It would be interesting to me to see what is going on in there for more reasons than one. I don’t have the answers.

I have put calls into the powers that be. I am hoping to have a follow up discussion with both Dr. Eames and Dr. Louis today.

It is a very interesting day of purpose.

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