As I said before, ASCO is fascinating to me because it doesn't just tell us where we've been (by looking back at how successful treatments have been over the past few years). But it's also fascinating because it gives us a glimpse of the future.
I've been looking at phase 1 clinical trials in the ASCO abstracts. As you may know, before a treatment can be approved, it goes through three different stages of clinical trials, each involving more patients. It can (and usually does) take years for a treatment to be studied enough to know that it is effective and safe.
Phase 1 typically involve a small number of patients, and focus on safety and "dose escalation" -- figuring out how much of a treatment to give to patients to that it is safe while being as effective as possible. Too much of something might kill more cancer cells, but also create more side effects that harm the patient so much that the effectiveness isn't worth it.
One of the interesting phase 1 studies I looked at was described in a presentation called "A phase 1 dose escalation and cohort expansion study of the safety and efficacy of allogeneic CRISPR-Cas9–engineered T cells (CTX110) in patients (Pts) with relapsed or refractory (R/R) B-cell malignancies (CARBON)."
This one is so new that it doesn't even have results yet. The presentation is a description of what they plan to do in the phase 1 study called CARBON.
The study will involve mostly Diffuse Large B Cell Lymphoma patients, but will also include Follicular Lymphoma Grade 3b patients, since FL 3b is often considered almost a separate, aggressive lymphoma, different enough from indolent FL that they're not even the same disease anymore.
What made me so interested in this presentation was its use of CRSPR technology. That's a pretty new technology, and worth some explaining. It's controversial in many ways, but exciting in many ways, too.
The idea for the study comes from what the researchers see as one of the weaknesses of CAR-T -- its use of autologous T cells (that is, taking T cells from the patient and changing them before putting them back). The problems include cost (it takes a lot of work to change the T cells), time (it can take a couple of weeks to take out the cells, change them, grow them into large enough numbers to be effective, and then put them back in the patient), and T cell failure (they don't do what they were supposed to, which is find and kill the cancer cells).
Another possible option would be allogeneic CAR-T treatment. Instead of taking cells from the patient, the cells are taken from someone else. They can be grown into huge numbers and kept available for use by any patient. So instead of waiting two weeks, the treatment could start almost immediately. And since they don't need to be specially made for each patient, they can be made more inexpensively.
The problem with using someone else's cells is that our bodies don't like to have stuff in them that doesn't belong there. This is what happens with Stem Cell or Bone Marrow Transplants. An autologous transplant involves removing a patient's stem cells, wiping out the immune system with aggressive chemo, and then putting the stem cells back in so they can grow quickly into immune cells and protect the patient. Auto SCT is usually safe but not always as effective as allogeneic SCT, which involves someone else's stem cells (often a relative). But the patient's body might reject the stem cells, since they see them as not belonging, the same way they'd see a bacteria or virus. It can be dangerous.
So if using another person's T cells for CAR-T has some advantages, how do you get past the potential problems?
CRSPR technology might help.
CRSPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Basically, CRSPR involves finding a segment of DNA in a cell, and then "editing" it by removing that segment and replacing it with another one.
Think of it this way. There's a small segment of DNA that controls the color of our eyes. Suppose we wanted our baby to have beautiful blue eyes, a tribute to Frank Sinatra. In theory, CRSPR technology could be used to find and remove that segment of DNA, and replace it so the baby had blue eyes.
That's the very controversial part of CRSPR technology, and there are huge ethical issues surrounding it. Used improperly, it could mean that some people are able to create people that are "perfect." That's not good. Lots and lots of problems there.
But not all uses of CRSPR are so potentially sinister. And that includes the one described here.
For the CARBON trial, researchers are working with previous studies to show that certain segments of DNA can cause problems with allogeneic transplants. By using CRSPR technology, they hope to change T cells by cutting out those problematic parts of the DNA and replacing them with DNA sequences that won't cause those problems. There won't be any use of CRSPR to change the patient receiving the cells.
The trial will involve patients with aggressive lymphomas, including FL 3b. They will be screened, then given a chemo regiment to wipe out most of the cancer cells, and then given CRSPR-manipulated T cells to wipe out the rest of them. And since T cells stay in the body and multiply when needed, if the cancer cells come back, the T cells will be there to go after them again. Patients will be followed for 5 years to see how well the treatment continues to work.
Will it work? I'm not sure. It will be interesting to see if there are positive results in the years to come. The researchers are continuing to recruit patients.
But the bigger lesson here, I think, is that CRSPR technology is going to become a big part of cancer research in the years to come. You might remember that last last fall and winter, I was a patient representative for a couple of programs that gave money to cancer researchers for their projects. There were several projects involving CRSPR technology in those programs (not necessarily for FL). We might not see results immediately, and they might not be for Follicular Lymphoma, but I think it's going to change things for a lot of cancer patients in the future.
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