NK Cells Deliver in First Patient

I woke up yesterday morning to find a mountain of email in my inbox. Ordinarily this would be a sign of a lot of work to do. But this was different. This mountain of email was congratulating a family that had a child that had just had a complete response in a brand new phase 1 clinical trial. While we see responses in phase 1 trials fairly often this one is particularly worth mentioning. First, we rarely see complete responses and, secondly, we rarely see this type of response in the very first patient on trial. (Actually the very first patient with neuroblasotma in the world to recieve Natural Killer cells.) Finally, this result is especially rare for children with relapsed high risk neuroblastoma. This was a family truly worthy of receiving congratulations. The true test will be to see if this response is replicated in other patients. However, if you are a parent of a patient that meets the eligibility criteria for this study it may very well be something that should be on your radar.

The recently opened trial is offered only at Sloan Kettering. The official title of the trial is "A Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma. As of this date there has only been one patient that has completed the study but, as I mentioned above, the results were impressive. In this trial patients with high-risk recurrent or persistent neuroblastoma are given chemotherapy (topotecan, cyclophosphamide, and vincristine), natural killer (NK) cells, and an antibody called 3F8. We already know that the high doses of chemotherapy are pretty effective in this population of children. We also know that 3F8 can also be effective for patients with marrow disease and, to a lesser extent, bony disease. There is a significant group that do not respond, however. 3f8 isn't believed to work for these patients because their immune systems lack sufficient (or capable) nature killer to fight it on their own, especially after chemotherapy. Less than 40% of children have this problem but it does give us an idea of why antibody does work in some patients but not others. By providing the patients with donor (allogenic) natural killer cells they are hoping to give the immune system enough of a boost that it will raise an attack against the neuroblastoma cells in these patients. In the first patient, it certainly looked like it did. It is tremendous news, especially for this patient.


I must admit I am somewhat surprised. I have actually seen quite a bit of preclinical research on NK cells and antibodies over the last two years. In animals, the combination seemed to improve response over either antibody or NK cells alone but the effect was not nearly as dramatic as what we saw in this first patient. From looking at the data one would assume a modest improvement but nothing like this. I expected it to be better than antibody alone. Just not this much.

So, this leads me to a quandary. I need to answer the question - why? I have a few theories which may lead to an answer and are probably worthwhile questions to ask your oncologist if you are considering this therapy. (I would be.) First, was this patient's response due to the preparatory regimen of high dose topotecan, cyclophosphamide, and vincristine? Quite possibly, however, I know nothing about the timing of this first patient's scans or previous response to these agents. Still, I would like to know more to try and ascertain the source of the success. Second, was the modest improvement that I saw in the preclinical research because they were looking at animals that did not have this immune system deficiency? I must admit, this is worth discussion but I think it is really more likely to produce speculation than answers.

In the end, the bottom line is this. If your child has refractory or relapsed disease, does not have heavy disease load (limited to bone and bone marrow), and may or may not have responded to antibody before, this is probably a worthwhile discussion to have with your oncologist.

Like I said, sometimes I am tremendously happy to find a mountain of email in my inbox.

Sometimes it is a sign of great purpose.