In a new study entitled “Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma,” researchers revealed results of a Phase I clinical trial testing a T cell immunotherapy in the treatment of HER2-positive sarcoma patients. The study was published in the Journal of Clinical Oncology.
A team of researchers at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital and Texas Children’s Cancer and Hematology Centers tested the efficacy of tumor-directed T cell therapy in patients with metastatic or recurrent sarcoma — a rare cancer that develops from certain tissues, including muscle, bone, nerves, cartilage, tendons, blood vessels and fatty and fibrous tissues. The team performed a phase I/II clinical study where patients with HER2–positive sarcoma (HER2 is short for human epidermal growth factor receptor 2, promotes the growth of cancer cells) received re-engineered T cells expressing HER2-specific chimeric antigen receptors (CAR).
The team tested increasing dosages (from 1 × 104/m2 to 1 × 108/m2) of therapy in both pediatric and adult patients with HER2–sarcoma, observing that HER2-CAR T-cell infusions into patients was well tolerated and without signs of toxicity, at any of the tested doses. The HER2-CAR T-cells were detected within 3 hours of infusion, with a minimum dose of 1 × 105/m2, and its levels were still detected after 6 weeks in patients treated with 1 × 106/m2 HER2-CAR T cells (in seven out of nine patients). The researchers also noted that tumors of two patients were positive for HER2-CAR T cells, suggesting the infused lymphocytes were specifically targeting tumor cells.
The results of this phase I/II clinical study show HER2-CAR T cells are both safe and effective, establishing the foundations for additional work to combine HER2-CAR T cells with other immune therapies to further enhance their anti-cancer potential.
Dr. Stephen Gottschalk, Professor of pediatrics at Baylor and study lead author commented in a press release, “Using T cells as immunotherapy for cancer is increasingly being explored over the last 10 to 15 years. But there have not been too many CAR T-cell therapy studies for solid tumors so far, particularly for cancers that express HER2. We’ve now shown that indeed HER2-CAR T cells are safe up to the highest dose level tested, and since HER2 is expressed in a broad range of cancers, we are hopeful that our approach can be further developed to benefit many patients. If you look at the history of cancer therapy, there are few examples of ‘magic bullets’ that can cure cancer alone,” Gottschalk said. “In general, combining different agents has proven most effective, and now we can think about different ways to explore this using HER2-CAR T cells.”