Are off-the-shelf CAR-T therapy options going to be commonplace in the near future? Or is that only a “pipe dream?” Given the high costs and lengthy time process to create CAR T-cells for cancer treatment, doctors and patients alike are hopeful that an off-the-shelf version of this promising immunotherapy will happen. But there are some risks associated with donor-derived “off-the-shelf” versions versus patient-derived CAR T-cells.
Chimeric antigen receptor T-cells or CAR T-cells have been approved by the US Food & Drug Administration (FDA) for the treatment of various B-cell cancers, solid tumors and non-Hodgkins lymphoma, along with some other types of cancer. Patients must have been through at least one previous round of treatment that was unsuccessful before attempting CAR-T therapy. The patients who receive CAR-T therapy are often terminal, sometimes with only months left to live without successful treatment.
Due to its success rate of between 30 and 40 percent in terminal cancer patients, CAR-T treatments are a last resort, as well as the greatest hope for patients. This is why the length of time that CAR-T therapy takes is such a large issue in the field of cancer research and treatment.
CAR T-cells are created by first drawing blood from a cancer patient and then separating the T-cells from the white blood cells. The T-cells then go through a lengthy process of genetic re-engineering. The T-cells are rewired so that they will recognize several specific antigens on cancer cells, and target them for extermination. Once that is accomplished, the T-cells are then mass produced before being re-infused into the patient’s body. The entire process can take three to four weeks to complete. In the 30 to 40 percent of patients for whom the treatment is successful, their cancers are thrown into remission or completely removed — sometimes for years.
T-cells taken directly from a cancer patient are called “autologous CAR T-cells.” When the T-cells are taken from a donor, however, they are called “allogenic CAR T-cells.”
Allogenic CAR T-cells are the “off-the-shelf” model mentioned above. Since they come from donors who are cancer-free, allogenic CAR T-cells can be mass produced ahead of time and are ready to administer immediately. Terminal cancer patients, who may only have months to live, do not have to wait three to four weeks for tautologous CAR T-cells to be produced before they can receive treatment. With off-the-shelf T-cells, no time is wasted during the lengthy production process.
However, there are downsides to donor-derived CAR T-cells versus patient-derived CAR T-cells. Many people have heard of graft versus host disease when it comes to the field of organ transplants. Sometimes a patient’s body rejects an organ that has been donated by someone else. The same graft versus host disease can occur with off-the-shelf CAR T-cells. While this is an issue, it does not seem to deter patients from being willing to try the therapy.
Allogenic therapy is also much less expensive than autologous therapy, making it an attractive option for patients. Pharmaceutical companies foot more of the costs for off-the-shelf treatments.
Clinical trials for various CAR-T therapy options are now heading into phase 2 trials. Doctors are hopeful that FDA approval for an off-the-shelf CAR-T treatment will be forthcoming very soon.