According to early results from an ongoing Phase I dose-escalation clinical trial, an innovative CAR T cell therapy called KIR-CAR has demonstrated safety and increasing effectiveness at higher doses in nine patients with advanced ovarian cancer, mesothelioma, or cholangiocarcinoma. The news was recently presented at the American Association for Cancer Research Annual Meeting.
Mesothelioma Patients Receive First-of-Its-Kind CAR T Therapy with Natural “On-Off” Switch
The mesothelioma trial is being conducted at the University of Pennsylvania’s Perelman School of Medicine, and its findings represent the first clinical data for the KIR-CAR therapy, which uses natural killer (NK) cell-like receptors to overcome T cell exhaustion and limit side effects in mesothelioma and other solid tumors. Dr. Janos L. Tanyi, principal investigator of the multisite STAR-101 Phase I Clinical Trial, presented the results.
“This is exciting because we’re seeing good efficacy signals, even at low doses, and limited toxicity in cancer types that have never had an approved cell therapy,” Tanyi said, referring to mesothelioma and other solid tumors treated in the trial. “As we continue enrollment and dose escalation, we hope to see more patients’ tumors responding to the therapy and continued persistence and longevity of the T cells, all with less side effects than conventional CAR T cell therapy.”
KIR-CAR Mesothelioma Cell Therapy is First of Its Kind
The KIR-CAR used in this mesothelioma study, SynKIR-110, targets mesothelin, a protein widely expressed on solid tumor cancers, including mesothelioma, and which has no or low expression on normal cells. It is the first of its kind to move forward into clinical trials. The design, based on NK cell receptors, is a “multi-chain” model that differs from the “single-chain” approach of traditional CAR T cells. In the new multi-chain model, antigen-binding and stimulatory functions are carried on separate chains. One chain directs the T cell to recognize the target on the cancer cell surface, and the other triggers an attack once the target is found. This allows the T cell to rest when not attacking tumor cells rather than constantly remaining in an active state.
Explaining the innovation further, Tanyi said, “The KIR-CAR design provides a natural ‘on-off’ mechanism, which helps avoid the problem of T cell exhaustion. …. Because it’s not continually ‘on,’ it also limits immune-related adverse events from the CAR T cells engaging with healthy cells. The mesothelioma clinical trial is enrolling patients with mesothelin-expressing cancers, including advanced ovarian cancer, mesothelioma, or cholangiocarcinoma, who have already received at least one prior standard of care treatment and experienced a relapse. These aggressive and/or rare cancers have limited effective treatment options, particularly after initial treatment failure. The mesothelioma research team is continuing clinical trial enrollment at Penn’s Abramson Cancer Center and three other sites, with 42 patients expected to enroll in the Phase I study.
If you or someone you love has been diagnosed with mesothelioma or another asbestos-related disease, this innovative research offers real hope. For information on other resources, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.
