CAR T-cell therapy is becoming a more accepted therapeutic approach. What is it?
Q: What is CAR T-cell therapy?
A: Our immune system protects our bodies from "invasion" by harmful substances, infections and abnormal cells (for example cancer cells). T-cells (also called T-lymphocytes or thymocytes) develop from stem cells in the bone marrow and mature in the thymus (a body organ in the neck that is part of the lymphoid system, along with the spleen, lymph nodes and the red bone marrow).
Cytotoxic T-cells identify body cells that have certain antigens (proteins on the surface of certain cancer cells, cells that have become infected, other cells) and directly kill them.
Helper T-cells detect various "invasions" and release cytokines to activate other immune system cells (including cytotoxic T-cells) to combat them.
Regulatory T-cells help moderate the immune response to maintain balance and the body’s ability to tolerate (rather than attack) itself (for example helping minimize inappropriate inflammatory responses).
This description of T-cells shows why it would be helpful to "manipulate" them in a specific manner to leverage the immune system to help fight certain diseases/conditions. This is where chimeric antigen receptor (CAR) T-cells come into play.
How do doctors create CAR T-cells?
White blood cells (including T-cells) are collected from the patient by taking some of their blood via an intravenous (IV) catheter and filtering out the white cells using a leukapheresis machine, and then putting the filtered blood (minus the extracted white blood cells) back into the patient via a second IV catheter.
The T-cells are then separated from the other white blood cells, and a gene for the "targeted" antigen is added to the cells (you can think of this as a "lock and key" mechanism, with the antigen being the "lock" and the protein added to the T-cell being the "key" used to identify the "invading" cell with that particular antigen "lock."
These modified cells (the CAR T-cells) are then "multiplied" in the lab to create a large number of them. The CAR T-cells are then infused into the patient (again via an IV). These CAR T-cells can now specifically "hunt" the specific "invading" cell(s) they have been created to target.
There are many steps needed to create this personalized CAR T-cell treatment for an individual patient, and therefore it can take weeks to produce these treatments. In the future it may be possible to pre-prepare treatments from donor T-cells (possibly modifying these cells to target specific antigens using techniques like CRISPR, mRNA techniques, etc.) and then transfuse the appropriate CAR T-cells in a manner similar to how other blood products (for example red cells, platelets, etc.) are transfused to help a patient.
Treating blood and other cancers
Since 2017 CAR T-cells have been specifically designed and utilized to treat individual patients with several different types of "blood cancers" (lymphomas, leukemias and multiple myelomas) that did not respond to the standard treatments (for example chemotherapy for that type of cancer). In many patients with very difficult to treat blood cancers, these treatments have been very effective.
Solid tumors (as opposed to blood cancers), such as brain, breast, lung and pancreatic cancers, are a bit more challenging to address with the CAR T-cell approach. This is because having the CAR T-cells gain "access" to the solid tumor cancer cells is more difficult.
From the description of T-cells above, it seems that this same conceptual approach might be utilized to treat certain autoimmune conditions (conditions where a patient’s own immune system "overreacts" and attacks the patient’s own body cells), and this has recently been studied. In this study, five patients with severe lupus who had not responded to standard treatments were treated with specifically designed CAR T-cells to "wipe out" the aberrant B cells causing their autoimmune complications, and all five showed very significant improvement. Future clinical studies will no doubt be designed to see what other conditions might benefit from this treatment approach!
However, treatment with CAR T-cells is not without risk, as these treatments can sometimes cause serious and even life-threatening complications. For example, some patients have had:
Cytokine release syndrome (CRS), where the patient reacts to the CAR T-cell infusion with an aggressive release of cytokines that causes an inflammatory reaction (for example causing symptoms like fever, breathing issues, gastrointestinal issues, other symptoms); nervous system issues (for example headaches, seizures, alterations in consciousness, others), and there may be many other possible complications.
The future of CAR T-cell therapy
Bottom line: CAR T-cell therapy has become a more and more accepted therapeutic approach, and in the future it may be utilized earlier in a patient’s disease (rather than only for refractory cases), and for a broader array of disease states (not just blood cancers, but potentially autoimmune conditions, maybe certain solid tumors, and potentially other diseases).
Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.
This article originally appeared on MetroWest Daily News: CAR T-cell therapy is new approach to fighting cancer, other diseases
