The FDA approved a CAR T-cell therapy for Orphan Drug Designation status. The therapy is called SynKIR-110, and it features a unique methodology for targeting the protein mesothelin. This protein is expressed in most cases of mesothelioma cancer. This designation should help advance the CAR T-cell therapy and test it in patients with malignant mesothelioma, ovarian cancer and cholangiocarcinoma.
SynKIR-110 is developed by Verismo Therapeutics, which is a biopharmaceutical spinout from Penn Medicine at the University of Pennsylvania. Penn Medicine’s Abramson Cancer Center is one of the top mesothelioma cancer centers.
“Mesothelioma is a rare and deadly disease for which few other treatment options currently exist,” said Bryan Kim, DMD, CEO of Verismo Therapeutics, in a Verismo Therapeutics press release. “We look forward to working with the mesothelioma community to advance SynKIR-110 as a potential treatment while we continue to expand clinical investigation of this novel platform in other cancers in the solid tumor space.”
What Is Orphan Drug Designation?
Orphan Drug Designation is given to new therapies for rare diseases. The designation provides funding to biopharmaceutical companies and medical institutions to develop treatments for rare diseases.
Orphan Drug Designation for malignant mesothelioma means a new therapy is showing potential and progressing through the approval process. For the CAR T-cell therapy in question, the treatment is ready for a phase 1 trial.
Orphan Drug Designation of new therapies is needed for mesothelioma due to poor survival rates. Most people survive for 1-2 years after they’re diagnosed. The 5-year survival rate is less than 10% for mesothelioma.
Ovarian cancer has a better prognosis for patients. The 5-year survival rate is closer to 50%, but patients need new therapies. Both mesothelioma and ovarian cancer are caused by exposure to asbestos fibers. Asbestos is the only cause of mesothelioma, while it’s one of many possible causes of ovarian cancer
What Is CAR T-cell Therapy for Cancer?
CAR T-cell therapy is a type of cell and gene therapy for cancer where doctors remove a patient’s T cells and alter them with new genetics to help find cancer cells. This type of cell and gene therapy is a targeted therapy, meaning the therapy targets a specific vulnerability of cancer.
T cells are a type of white blood cell in the immune system. The body uses T cells to react to the presence of viruses, diseases and infections. Cancer is also a responsibility of T cells, but cancer often subdues the T cells and tricks them into ignoring the disease.
T cells also have other directives and sometimes don’t focus enough on looking for cancer cells. CAR T-cell therapy fixes these challenges.
Using Gene Therapy to Enhance the Immune System
The new genes added to the removed T cells create a new protein receptor on the exterior of the cells. This new protein receptor is linked to a protein expressed on the patient’s cancer.
Doctors then multiply the new CAR T cells and create millions of them, which are infused back into the patient’s bloodstream. The engineered T cells then begin seeking out any cells with the target protein linked to the T cells’ new protein receptor.
CAR T-cell therapy is a leading type of cell and gene therapy, which is within the class of cancer immunotherapy. There are six CAR T-cell therapies approved for blood cancers like leukemia, lymphoma and multiple myeloma. As of October 2022, there are no CAR T-cell therapies approved for solid tumors like mesothelioma.
What Is SynKIR-110 CAR T-cell Therapy?
SynKIR-110 is called a KIR-CAR therapy. It uses a dual-chain platform that is unique to other CAR T-cell therapies. Aside from targeting mesothelin, the KIR-CAR therapy targets DAP12 to improve T-cell stimulation against mesothelioma cancer.
The therapy can be combined with other technologies, including in-vivo gene editing. The medical term “in-vivo” means “in the patient” or “in the body.” In-vivo gene editing is technology to edit the genes of T cells without removing them.
Another technology possible with SynKIR-110 is allogeneic cell therapy, which is using healthy donor T cells to make T-cell therapy instead of relying on the patient’s T cells.
SynKIR-110 will be part of a phase 1 clinical trial titled “STAR-101” for people with mesothelin-expressing mesothelioma, cholangiocarcinoma and ovarian cancer. The trial is expected to begin accepting patients early in 2023. It’s a first-in-human clinical trial assessing safety, tolerability and tumor response from the SynKIR-110 therapy.
Sources & Author
- FDA Grants Orphan Drug Designation to SynKIR-110 for Mesothelin-Expressing Mesothelioma. OncLive. Retrieved from: https://www.onclive.com/view/fda-grants-orphan-drug-designation-to-synkir-110-for-mesothelin-expressing-mesothelioma. Accessed: 10/07/2022.
Sources & Author