New Ways to Use Our Own T Cells to Treat Myeloma
Most of us have been reading about CAR-T treatments over the past few years to treat a variety of hematological malignancies. Two CAR-T products have been on the market for nearly two years now to extend survival of patients with several different lymphomas as well as pediatric acute myeloid leukemia. You may also be aware of the regulatory submissions by Johnsen and Johnson (marketers of Darzalex) and Bristol Myers/Celgene (makers of e.g., Pomalyst and Revlimid) of their own CAR-T products targeting MM. We hope that both of these last two products will see FDA approval either late this year or early next year.
A quick reminder of what CAR-T is may be in order. T-Cells are harvested from individual patients, engineered with the insertion of a viral vector that allows them to attach to specific surface proteins on MM-cells, and are then expanded in a process that yields large quantities of the engineered cells for infusion back to the original donor patient.
An interesting article was published over the past week in the journal Science Translational Medicine. This article introduces us to the world of ‘autologous multitumor-associated antigen specific T-cells (mTAA)’.
Let’s explain the different parts of this mouthful. We have heard/know about T-cells. Autologous is also familiar to us : these are our own cells (not donor cells). The very short, very incomplete and overly simplistic definition of an antigen is a molecule or molecular structure that can be bound to an antigen-specific antibody or antigen receptor present on the surface of cells. [Those who wish to learn more can always go to Wikipedia where antigens are explained more thoroughly.] Multitumor and specific are somewhat self-explanatory in the sense that we are looking for T-cells that can bind to a number of different, but specific, targets on the myeloma cell.
In other words, the idea here is to find T-cells of our own that already naturally express a variety of different antigens that can hook onto a number of different targets on the surface of myeloma cells so that the T-cells can do their job of killing the cancerous cells. This is different than what we are currently familiar with in CAR-T for MM. For example, the two products currently under FDA review, mentioned earlier, target the myeloma cell surface protein BCMA. In the not too distant future, we will also be seeing multiple myeloma CAR-T products that will be bi- or tri-specific (targeting two or three different surface proteins).
The article just published discusses T-cells that are specifically screened to have the presence of five different antigens, that can target any one or more of five antibodies present on MM-cells, latch on to them, and do so without having to be engineered with viral vectors. This means that the expanded cells can be made available back to the patient faster than can currently be done with the CAR-T process. The article mentioned above presents the first data from a small (21 patients) clinical study. Nine patients were at high risk of relapse and 12 had active, relapsed or refractory disease after a median of 3.5 lines of prior treatments. No long-term follow-up data are available yet, but the early results are encouraging. Patients tolerated the infusion well, only 10 % of patients had transient infusion related adverse events (better than CAR-T treatments as we currently know them). The patients with active, refractory/relapsed disease all enjoyed longer progression free survival than expected. I realize that you may be looking now for ‘hard’ numbers, but, unfortunately, we will have to wait until the longer-term follow-up data will be published in the future.
Either way, this is novel MM-technology to keep an eye on in the future to give us a treatment alternative that may be EASIER on the patient than CAR-T, and may therefor become an alternate choice for patients that are more frail. We are some years away still for this type of treatment to go through the full clinical and regulatory process, but chances are fairly decent that we may be looking at something with good future potential to give us added hope in fighting our disease.