Tumors in Mesothelioma Patients Reduced by T Cell Receptor JTCR016

Evidence that T cell receptor product JTCR016 can reduce the size of mesothelioma tumors was presented recently at the American Association for Cancer Research (AACR) annual meeting in New Orleans, Louisiana.

This same evidence also showed that JTCR016 can spur significant T cell expansion and persistence in mesothelioma patients. JTCR016 targets Wilms tumor-1 (WT-1), according to the presenters.

These findings were made by the company that manufactures JTCR016 and were obtained in collaboration with other researchers. The company that produces JTCR016 is Juno Therapeutics, Inc. of Seattle, Washington.

The JTCR016 evidence was presented at the AACR meeting by Phil Greenberg, M.D., who is in charge of the immunology program at Fred Hutchinson Cancer Research Center in Seattle. Greenberg is also a professor of medicine, oncology and immunology at the University of Washington.

Targeted Refractory Mesothelioma

Greenberg’s presentation was titled, “Targeting Cancer with Engineered T Cells.” He discussed JTCR016’s use in WT-1 T cell receptor therapy for both refractory mesothelioma and acute myelogenous leukemia.

Greenberg explained that JTCR016 was investigated as part of a combined Phase I and Phase II study. The aim of this combined study was to explore the capabilities of genetically modified T cells. These T cells were engineered to target WT-1 in WT-1-expressing mesothelioma and in non-small cell lung cancer.

Five patients were enrolled in this study. Three had been treated by the time of Greenberg’s presentation to the AACR.

According to Greenberg, the preliminary data show that one of the mesothelioma patients experienced a partial response to treatment with JTCR016. Moreover, this response was ongoing. A second mesothelioma patient achieved stable disease status as a result of treatment with JTCR016.

Greenberg said these responses seemed to be in keeping with the pharmacokinetics of the engineered T cells. He added that the partial response achieved with JTCR016 was particularly encouraging because the patient’s mesothelioma had earlier progressed despite having been treated with chemotherapy and radiation.

Greenberg announced that all three mesothelioma patients tolerated JTCR016. None exhibited severe cytokine-release syndrome or severe neurotoxicity.

Mesothelioma Treatment Is Part of Larger Family

Mesothelioma treatment JTCR016 belongs to Juno’s chimeric antigen receptors (CAR) and T cell receptor (TCR) technologies. The company says these products are genetically engineered to identify and then destroy cancer cells.

Juno’s CAR T cell technology is premised on the insertion of a gene for a particular CAR into the T cell. This allows it to recognize cancer cells based on the expression of a specific protein located on the cell surface, the company has said.

Meanwhile, its TCR technology “provides T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell,” according to Juno. “When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell.”

JTCR016 is only an investigational product at this stage, the company stresses. Its safety and efficacy have yet to be established.

Both the CAR and TCR product lines reflect Juno’s goals of “building a fully integrated biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer.”

The company’s research partners include Fred Hutchinson Cancer Research Center, Memorial Sloan Kettering Cancer Center, Seattle Children’s Research Institute and The National Cancer Institute. The company also is the licensor of a CD19 gene product being tested by St. Jude Children’s Research Hospital.