The Future of Sarcoma Therapy: Genetically Engineered T-Cells?

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The Sarcoma Alliance Takes Notice of New Immunotherapies Studied As Potential Treatment for Sarcoma, a Rare Cancer of Connective Tissue

Genetically engineered T-cell therapy, a form of immunotherapy, promises to dramatically change the way physicians treat disease, including sarcomas.

The Sarcoma Alliance is hopeful that state-of-the-art immunotherapies like genetically engineered T-cells may someday be routinely used in the treatment of sarcoma. One biotech company, Adaptimmune, is heading down this path with a clinical trial for sarcoma patients.

At the American Society of Clinical Oncology’s 50th annual meeting, Adaptimmune announced that it had struck a deal worth $350M with the large drugmaker, GlaxoSmithKline, to develop its cancer therapies. Adaptimmune, a US- and UK-based biotech company, is currently running a clinical trial for their genetically engineered T-cell therapy in patients with unresectable, metastatic, progressive, or recurrent synovial sarcoma. Synovial sarcoma comprises 8% of all soft-tissue sarcomas, and is characterized by a specific genetic signature. According to, Adaptimmune’s Phase 1 clinical trial, with sites at the National Institutes of Health and at the Children’s Hospital of Philadelphia, is still recruiting patients.

Genetically engineered T-cell therapy, a form of immunotherapy, promises to dramatically change the way physicians treat disease, including sarcomas. Currently, when a sarcoma cannot be treated by surgery alone, chemotherapy is used. Chemotherapy is typically a combination of “toxic” small molecules, such as doxorubicin and ifosfamide, which treat the cancer but can also hit healthy cells and tissues, resulting in numerous side effects. By contrast, immunotherapy uses the patients’ own immune system to treat the disease. Because cancer is made up of the body’s own cells, it can usually “hide” from the immune system. Immunotherapy retrains the patients’ own immune system to attack the disease.

For Adaptimmune’s genetically engineered T-cell therapy, patients have their own white blood cells removed by a physician. A new gene is then inserted into the T-cells from this sample to make these T-cells more active against sarcoma cells expressing a certain antigen, NY-ESO-1. Because this antigen is tumor-specific, the genetically engineered T-cells, when re-injected into the patient, are active only against the sarcoma tissue. Results from a pilot clinical trial of related technology in metastatic synovial sarcoma and melanoma demonstrated clinical response in 67% of synovial sarcoma patients and 45% of melanoma patients, with 2 of the melanoma patients demonstrating complete regressions that lasted more than 1 year. Adaptimmune is also running clinical trials for their genetically engineered T-cell technology in myeloma, ovarian cancer, melanoma, hepatic cancer, and HIV.

While it will still be many years before immunotherapies like these genetically engineered T-cells are regularly used in the treatment of sarcoma, it is exciting to see biotechnology companies taking on the challenge of treating this rare disease, and the backing of a large pharmaceutical company will certainly help get unique treatments like this one into the clinic.

Written by Dr. Erika Stanzl


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Alison Olig

Erika Geihe Stanzl
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