An oncologist provides insight on his experience with using CAR-T therapy in the clinic and his prediction for the future of this revolutionary treatment.
Published Online: February 16, 2017
Surabhi Dangi-Garimella, PhD
EBO™: This form of T-cell treatment could be considered an ‘N-of-1’ trial. Will the FDA evaluate this treatment differently, compared with the regular drug approval process?
Park: I think the FDA is viewing this therapy quite favorably because they recognize that for some of the diseases that are being studied, there currently are no good alternatives for treatment. There are some regulatory processes involved, because this treatment is categorized as a gene therapy due to the use of a retroviral or lentiviral vector for modifying the genetically engineered T cells. But the treatment has already received a breakthrough treatment designation for ALL and is close to being approved, as long as its efficacy and safety are confirmed in the ongoing large phase II clinical trials.
EBO™: Are combination trials of CAR-T cells with immune checkpoint inhibitors being planned in the near future?
Park: CAR T-cell therapy, especially in ALL, is very effective and patients can get into remission 80% to 90% of the time, which is why we are so excited about this treatment. But it’s not perfect, and not all patients benefit from it, and even after the initial respons, relapses do occur. So there’s more work needed to overcome some of these challenges, and combining CAR T-cell treatment with one of the immune checkpoint inhibitors might be one way. It could help prolong the immune response, prolong the persistence of the T cells, and hopefully prolong the duration of response.
These treatments are being evaluated at some of the centers around the country. Currently, we do not have enough data to draw conclusions on whether the combination of CAR-T cells with immune checkpoint inhibitors will be effective or whether it would result in more side effects. There are some safety mechanisms and management guidelines with these type of trials, but it’s definitely a natural next step that we are currently exploring.
Next-generation CAR-T cells are also being explored in clinical trials—these cells are made stronger even without the immune checkpoint inhibitors.
EBO™: What is your prediction about where the future lies for CAR-T cells in oncology care?
Park: We are obviously very excited about the tremendous impact of immunotherapy in cancer care. Moving from chemotherapy, which is very nonspecific, to oral targeted treatments that target specific pathways—cancer cells do become resistant to these treatments. With immunotherapy, we are not targeting any particular signaling pathway; rather we are manipulating the body’s immune system to better recognize and kill cancer cells.
So, the future, I think, is very bright and we are very close to getting this therapy approved in patients with ALL, using CD19-targeted CAR T-cells. We do have a lot of unanswered questions, such as whether treatment efficacy will remain the same with solid tumors and if not, whether we can improve efficacy with next-generation CARs or by combining the treatment with immune checkpoint inhibitors or with oral-targeted therapy.
A lot of efforts are being invested to improve the safety and efficacy of CAR-T cells, so we do expect the emergence of better and safer therapies in the future, either in combination treatments or by further modification of CAR-T cells, to hopefully lead us to a “cure” for cancer. I believe CAR-T cells is one of the ways by which we can get there.