Follow-Up #16

I am still NED, and still very, very grateful to be cancer-free and healthy.

We brought our three sons with us on the drive this time, and had a fun time touring the Smithsonian and other D.C. spots. As it was very early in March, the pandemic had not yet compelled us to stay in our homes.

My visits are officially going to be only annually from now on. I am glad for that.

I ran across some interesting reading in the book "Darwin's Black Box" this week. It sheds new light on what could be the reason that a fourth cell showed up in my post-treatment bloodwork shortly after I had TIL therapy.

Some background:  When I returned to NIH for the lobectomy in April 2016--almost a year subsequent to treatment with TIL, the Lab Guru visited me in my room to talk about what he was learning about my case. The scientists had known about three types of T-Cells that were included in the treatment bag on July 1, 2015. Around 70% of those TIL were known to be of a particular variety. What they found in subsequent blood-draws (post-TIL therapy) was a different population of cells, also reactive to the KRAS G12D mutation. "What does it mean?" I asked at the time. "We are not sure..." he had said.

Here's what biochemist Michael Behe wrote in his 1996 book that popped out at me yesterday while I was reading: "When a cell binds to foreign material, it receives a signal to replicate; during many rounds of replication the cell 'intentionally' allows a very high level of mutation in just the variable regions... This produces variations on a winning theme. Because the parent cell coded for an antibody that already was known to bind pretty well, mutating the sequence might produce a stronger binder. In fact, studies have shown that antibodies produced by cells late in an infection bind much more tightly to foreign molecules than antibodies produced early in an infection."

Could mutation be the reason the Lab Guru found that my circulating T-cells--post-treatment--had a much higher percentage of a new, and unexpected fourth cell? He said that the initial population had diminished to "almost nothing" but that my circulating blood still retained a "crazy high" amount of these new cells.

Update: Nope. The author was talking about B-Cells, which can adapt themselves in a way that T-cells cannot. However, a report by the Proceedings of the National Academy of Sciences makes the T-cells in my case a bit more clear (make sure you check out the corrections--some data was transposed in the original article). Four types of TCRs were found. TCR9a was the one most prevalent in the infusion product (~50%), but could not be found in my 9-month-post-TIL blood draw. TCR10, however, was a different story. That guy made up 20% of  the infusion product and remains at a whopping 10% in my circulation (as of March 2016). The other two were each present in the infusion product, though one was not found there until months later (using a banked sample). TCR9b and -9c were present in the infusion product at 0.04%, and 6.9% respectively, and 0.005% and 4.5% respectively at the 9-month blood draw. These data are in the article linked above, and also in the Supplementary Appendix of the NEJM article about my case.

I remember Dr. Tran saying of this cell at the time, "It's very particular about what it binds to. It will only bind to chains that are ten mers long--no others fit." (Update: He was talking about the persistent one, TCR10, not the "new" one.)

The Lab Guru has moved on, so I've got no one to ask my questions anymore. EDIT: My medical student daughter tells me that this property of immune cells is well-known--just not to me, until now.
: )

I have this verse on endless loop:
I praise you because I am fearfully and wonderfully made;
your works are wonderful,
I know that full well.Psalm 139:14