The first participant has been dosed in a Phase 1 clinical trial evaluating Tmunity Therapeutics‘ CAR T-cell therapy, CART-TnMUC1, in people with certain solid tumors, including ovarian cancer, that are positive for the TnMUC1 protein.
The open-label trial (NCT04025216), which is still recruiting, is expected to enroll about 80 people with previously treated cancers that express TnMUC1. Participants are being enrolled at The Angeles Clinic and Research Institute in California and the Hospital of the University of Pennsylvania.
T-cells are immune cells that are capable of killing cancer cells. When tumors do develop, it essentially means that the cancer cells have found ways to evade destruction by T-cells. Chimeric antigen receptor (CAR) T-cells are T-cells that are modified in a lab such that they have extra receptors that help them identify and kill the tumor cells.
Typically, CAR T-cell therapy involves taking T-cells from a cancer patient, modifying them in the lab, and putting them back in the patient’s body to fight the tumor. While these therapies have shown promise in certain blood cancers, they have generally not been very effective when tested in solid tumors.
MUC1 is a glycoprotein — a protein with sugar molecules attached to it — that is normally produced by the cells that line many glands in the body. When these cells become cancerous, however, they tend to instead express an altered version of the protein — TnMUC1.
CART-TnMUC1 is a CAR T-cell therapy in which the cells have been modified with a receptor specific to TnMUC1.
The idea behind the therapy is to target the killing action of the T-cells toward this altered version of the protein and, by extension, the cancer cells. The modified receptor also includes a co-stimulatory region called CD2, which helps activate the T-cells to mount a cancer-killing immune response.
“The major challenge in the field of CAR-T cells is targeting solid tumors, and we have great hope that we have potentially identified a new therapeutic approach,” Avery D. Posey, PhD, a professor at the University of Pennsylvania who helped develop CART-TnMUC1, said in a press release. “Our approach, testing these ‘sweet CARs,’ is to target a sugar that is uniquely expressed in tumor cells, with the aim to develop a more effective cancer therapy.”
The Phase 1 study will be conducted in two phases. The first part will include about 40 participants with metastatic ovarian cancer, pancreatic ductal adenocarcinoma, triple-negative breast cancer, non-small cell lung cancer, or multiple myeloma. They will be given a lymphodepleting chemotherapy regimen meant to prepare the body for the CAR T-cells, followed by different single doses of CART-TnMUC1.
The aim of this phase will be to identify the dose-limiting toxicity — that is, the maximum dose that can be given without unreasonable risk of serious side effects.
The second phase of the study will be conducted in about 40 participants with ovarian cancer that expresses TnMUC1 and is resistant to platinum-based chemotherapy. This phase is aimed at providing a preliminary evaluation of efficacy, measured by the proportion of patients achieving a response to treatment.
Other outcomes, such as safety, tolerability, time without disease worsening or death, and overall survival, will also be assessed.
“The initiation of the first trial to dose a patient with a CART-TnMUC1 represents an important milestone not only for Tmunity, but for the oncology community,” said Usman Azam, MD, president and CEO at Tmunity. “We look forward to progressing our portfolio of innovative cell therapies for high unmet need in solid tumors and advancing the potential for CAR-T therapeutics.”
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