Yesterday, the scientist in charge of some of the big science behind my TIL cell therapy took us on a tour of his lab, as well as a flyby of the TIL Cell lab, where they are growing my wee little TIL cells to their full robustness (ca. 30-100 billion cells at the end of the process). (I did secure permission to mention his name and use of these photos, for noncommercial purposes such as this blog.) Dr. Eric Tran, Ph.D., Postdoctoral Fellow, Surgery Branch, Tumor Immunology Section was kind enough to spend an hour walking us around and talking through the biology of what Dr. Rosenberg’s group is hoping to do for me.
As is the case with most bio labs I’ve seen, at first glance there’s not all that much to look at. Everything important is happening in little dishes inside of incubators. But there’s still cool science stuff sitting around, and cool science people doing cool science things. And since this science has a great deal to do with the current attempt to extend my life and wrest more time from the thieving arms of cancer, I was very glad to see what I could see and learn what I could learn.
Dr. Tran showed us the door to the lab where my main cultures are growing right now. They are culturing both my B cells and TIL cells. The B cells are in part to provide a medium for the TIL cells, and part to do Science!!! with me as the human petri dish. The lab is off-limits for non-workers, for reasons of safety and sterility. (The cell cultures’ safety and sterility, not ours.)
He then took us down to another lab where other human TIL cells are being cultivated for experimental work rather than clinical treatment.
There we saw TIL cells in their media packages within the incubator, as well as under an optical microscope. This was pretty cool, as we saw the difference between activated and inactivated TIL cells.
Lisa Costello, learning something.
That distinction between inactive and active is one of the things on which this whole treatment concept hinges. Healthy human TIL cells can be found interpenetrated with many kinds of tumor tissue. They have an affinity for tumors, which allows them to locate and invade the tumor. But the cancer has an ability to inactivate them, or leave them inactivated, depending on the situation. In effect, the cancer can turn these immune cells off.
Dr. Rosenberg’s group, through the work of researchers such as Dr. Tran, have found that the TIL cells can be reactivated. Once turned on, they will then attack the cancer cells which they previously interpenetrated on a quiescent basis. This works in the mouse model. This works in the petri dish with human cells. This works in some human cancers, such as melanomas. Dr. Tran’s area of study is how this might work in digestive cancers, such as my metastatic colon cancer.
What they did after last Thursday’s surgery was mince most of the retrieved tumor tissue down to very fine pieces, a few millimeters in diameter at most. This is still much larger than the relevant cells, so most were not damaged. The tumor chunks were then placed in a medium which is very friendly to TIL cells. My TIL cells began outmigrating from the tumor chunks at a vigorous rate. Dr. Tran felt this was a good sign, which was also a comment made by my two primary doctors, Dr. Klebanoff and Dr. Klemen. My B cells derived from my recent apheresis have also been cultivating well. This makes all three of them hopeful for the next steps.
Where things get kind of different for me is that thanks to all you folks out there in the world, I brought my own Whole Genome Sequencing (WGS) data to the party. In that data, the researchers found that my colon cancer has over 100 mutations, which is somewhat higher than normal, but not freakishly so. In identifying these mutations, the researchers can add an extra step to their protocol which they’ve only ever been able to do once before, and never with WGS data. That is to say, Dr. Tran will introduce those mutations specific to my cancer genome to my own B cells, then assessing whether my TIL cells react to any of the mutations as expressed in those B cells.
In effect, Dr. Tran can select from among my TIL cells for those mostly likely to target known mutation sites in the cancer’s genome, and thus attack only the cancer cells in my body. This adds a layer of genomic medicine to the already distinctly high-tech immunotherapy which is being studied in this protocol. He can then be sure that Dr.s Klebanoff and Klemen are working with the best possible pool of TIL cells to put back into my body in the infusion phase of the protocol.
This is about as cutting edge as it gets. The one other patient they tried this was someone they were able to do an Exome Sequencing run on, which can be critically valuable. I’m the first patient ever to bring the sequencing data in the door with me. And with my WGS data, Dr. Rosenberg’s team has the keys to the kingdom.
So Dr. Tran is using Big Science and Big Data to build the most efficient TIL cell infusion possible for Drs. Klebanoff and Klemen to go after my cancer.
The downside, such as it is, is that this filtering and selection of my TIL cells may add as much as a week to my TIL cell infusion start date, and may keep me in the NIH hospital as much as a week longer than we originally anticipated.
It doesn’t get much cooler than this. New doors in immunotherapy and genomic medicine are being opened by my case, with your support, first of the Sequence a Science Fiction Writer fundraiser last year, and ongoing right now the Science Fiction Author on Trial (NIH trial, that is!) fundraiser. Even though we’ve met goal on the new fundraiser, the targeted mutation screening step has added several thousand more dollars to our costs by extending our stay in Maryland, so every dollar helps.
By reading, by promoting, by donating, by supporting, this community of my friends and fans and readers and genre folk and cancer activists and patients and caregivers have helped slap down a big old paving stone on the path to better, more effective cancer treatments. I’m out at the pointy end of the stick right now, being helped by Dr. Tran and Dr. Klebanoff and Dr. Klemen and Lisa Costello and Dad and my family and friends, but none of us would be out here on the stick without you.
Thank you so very much.
I’ll leave you with this final thought from the hallway outside the labs.
Photos © 2008, 2014, Joseph E. Lake, Jr. All photos taken with permission.
This work by Joseph E. Lake, Jr. is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 United States License.