
Transforming Leukemia Treatment: ‘Off-the-Shelf’ CAR-T Cells Offer Lifeline to Patients
Transforming Leukemia Treatment: ‘Off-the-Shelf’ CAR-T Cells Offer Lifeline to Patients
August 11, 2023 | Dr. Lana du Plessis |
August 11, 2023 | Dr. Lana du Plessis |
It is not surprising that some of the most common tumors, referred to as “cancer of the blood,” have some of the most devastating consequences on patients, and are unresponsive to current treatments. For many years, the cornerstones of cancer treatment have been surgery, chemotherapy, and radiation therapy. Although these are still the most common treatments, new branches of treatment have transformed the survival rate of these cancer patients over recent years.
The 21st century marked the arrival of dozens of targeted therapies using drugs that find and kill cancer cells by seeking out specific changes found only on the outside of cancer cells. Despite these changes, the success of survival in patients was not much higher than with standard therapy.
Fortunately, over the two past decades, immunotherapy (therapies that recruit and strengthen the power of a patient’s immune system to attack tumors), has rapidly become what many call the “fifth pillar” of cancer treatment. These therapies include three “big names”, i.e., immune checkpoint inhibitors, TCR- (T-cell receptor), and CAR-T cell (Chimeric Antigen Receptor) Therapy (1).
How Does CAR-T Cell Therapy Work?
CAR-T cell treatment is a novel therapy whereby a person’s own immune cells kill cancer cells. After some blood is taken from the patient, the T-cells, a type of immune cell, are removed from the sample. Using cutting-edge genetic techniques, these T-cells are re-engineered in the laboratory to produce proteins on their surface called chimeric antigen receptors, or CARs. The CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells. Thus, the CARs program the T-cells to find and destroy cancer cells when injected back into the patient.
CAR T-cell therapy can be compared to a policeman, with a photograph of the criminal, being able to identify them on the street”. “It is an artificial way of guiding those cells to cancer when the cancer cells are in suspension. (2).
Presently, available CAR-T cell therapies are tailored for each individual patient. Since 2017, six CAR-T cell therapies have been approved by the Food and Drug Administration (FDA). All are approved for the treatment of blood cancers, including lymphomas, some forms of leukemia, and, most recently, multiple myeloma.
Notwithstanding the interest in these therapies, less than 50% of the patients treated with CAR-T cell therapy will survive longer than 5 years. There is also disapproval of their cost, which, can amount to more than $450,000. There have been more than 800 CAR-T cell clinical trials registered to date. The most successful CAR-T cell therapies have been in B-cell malignancies.
For now, all the CAR-T therapies that have been authorized by health authorities are produced from the patient’s own T-cells (autologous). The T-cells from the same patient, however, have some problems, especially in terms of the quality and quantity of T-cells that are produced by the patient, which may be insufficient. This in addition to the very high cost of autologous therapies makes it difficult to scale up production and improve the time of production.
How to overcome CAR-T drawbacks?
To overcome these drawbacks, many believe the answer will be the development of an “off-the-shelf” product derived from banks of a healthy donor’s(not the patient’s own) CAR-T cells or “allogeneic” CAR-T cells. Although they are generally made from adult Peripheral Blood (PB) T-cells, CAR-T cells could also be generated from Umbilical Cord Blood (UCB)-derived T-cells (3,4).
The development of novel cell therapy products from UCB could be the answer, as it might diversify the activities of UCB banks. In addition, these cells are tweaked further using another gene-modifying technology — “CRISPR” — to ensure they are not rejected by the patient’s own immune system. Additionally, UCB contains T-cells that have more adaptable immunological and phenotypic properties, the UCB CAR-T cells will induce fewer graft-versus-host-diseases (GVHDs), will have fewer HLA matching restrictions, which ease the requirements for a match between the donor and recipient, will provide long-term persistence and efficiency. The production of UCB-derived CAR-T is still in its infancy, but it presents many supposed advantages.
Although CAR T-cell therapies have shown the same ability to eradicate very advanced leukemia’s and lymphomas and to keep the cancer at bay for many years, Some of the advanced leukemia patients don’t have months or years to live, they merely have weeks. Therefore, using a “universal off the shelf” UCB CAR-T cell therapy, the wait may be even shorter. All it will require is the time needed to thaw the prepared frozen CAR-T cells for use in a transplant.
Reference:
- Sheykhhasan, M., Manoochehri, H. & Dama, P. Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study. Cancer Gene Ther 29, 1080–1096 (2022). https://doi.org/10.1038/s41417-021-00418-1
- https://www.drugtargetreview.com/article/57987/tcr-therapy-an-attractive-alternative-to-car-t/
- Caël, B.; Galaine, J.; Bardey, I.; Marton, C.; Fredon, M.; Biichle, S.; Poussard, M.; Godet, Y.; Angelot-Delettre, F.; Barisien, C.; et al. Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells. Cancers 2022, 14, 3168. https://doi.org/10.3390/cancers14133168
- https://www.onclive.com/view/orca-t-leads-to-100-survival-rate-in-early-trial-of-patients-with-hematologic-malignancies-and-7-8-mismatched-donors