Recent advances in developing cellular therapies, a broad group of strategies that use cells to treat disease, have shown efficacy in some types of blood cancer. Chimeric antigen receptor T (CAR T) cells, treatments involving manipulating a patient’s immune cells to make them more effective in killing cancer cells, can elicit between 40 – 90% response rates. However, researchers have faced challenges in optimizing these approaches to treat solid tumors.
Recent developments in T cell receptor (TCR) engineered T cells, another form of cellular therapy, have resulted in an apparent ability to target antigens inside cancer cells. This characteristic could prove valuable in treating solid tumors with cellular approaches. Despite the promise of TCR T cell therapies, most clinical trials show only modest clinical efficacy. However, a recent study published in Nature Medicine presents some encouraging data.
The interim report details a multicenter phase 1 clinical trial (NCT03686124) assessing the safety of TCR T cells targeting PRAME, an antigen expressed in some cancers, including melanoma and sarcoma. The treatment, IMA203, involves removing a patient’s own immune cells, engineering them in a laboratory setting to recognize PRAME, and returning the immune cells back to the patient with an optimized ability to find and kill PRAME-expressing melanoma cells. Because the engineered cells include enhanced targeting and killing capabilities, optimization of this approach could be a game-changer for targeting hard-to-treat cancers.
The study, which included 40 patients, demonstrated the safety of the treatment. Only 4.9% of the patients experienced severe cytokine release syndrome, a condition characterized by the release of immune factors into the blood. Importantly, no cases of severe neurotoxicity, treatment-related damage to the nervous system, signaling the safety of the approach.
IMA203 induced an overall response rate of about 52%, including a roughly 30% confirmed response rate, which refers to the proportion of patients who showed a positive response to the treatment that was later confirmed by additional tests or observations. Treatment responses lasted, on average, 4.4 months, with some responses ranging to over 20 months. In addition, the researchers monitored the durable persistence of IMA203 T cells, observing T cells that persisted for more than 700 days post-treatment.
The study showed that higher doses resulted in a greater chance of confirmed responses. Further, T cells remained active and did not show signs of exhaustion. The researchers reported that T cell infiltration predicted longer progression-free survival.
The data presented at the interim point of this study hold great promise for advancing the field of cellular therapy. The potential benefits of this treatment could help patients with solid tumors, a group that currently has limited cellular immunotherapy options.
Sources: Blood Adv, Front Immunol, Nat Med