Reviewed By: Robert Maki, M.D., Ph.D.
Robert Maki, M.D., Ph.D., Professor of Medicine, Pediatrics, and Orthopaedics, Mount Sinai Hospital, New York, NY
Sarcoma is one of the major cancer types for which new immune-based cancer treatments are currently in development. This page features information on sarcoma and immunotherapy clinical trials for sarcoma patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based cancer treatments to people with sarcoma.
A sarcoma is a cancer that arises in the body’s connective tissues, such as muscle, fat, bone, or cartilage. Sarcomas are given a number of different names based on the type of tissue that they most closely resemble. For example, osteosarcoma resembles bone, chondrosarcoma resembles cartilage, liposarcoma resembles fat, and leiomyosarcoma resembles smooth muscle.
There are approximately 15,610 new cases of sarcoma diagnosed per year in the United States, and 6,480 deaths. Sarcomas represent about one percent of the 1.7 million new cancer diagnoses in the U.S. each year. Gastrointestinal stromal tumor (GIST) is the most common form of sarcoma, with approximately 3,000-3,500 cases per year in the United States.
Sarcoma is a rare cancer in adults (1% of all adult cancers), but rather prevalent in children (about 15% of all childhood cancers). Some sarcomas, such as leiomyosarcoma, chondrosarcoma, and GIST, are more common in adults than in children. Most high-grade (aggressive) bone sarcomas, including Ewing sarcoma and osteosarcoma, are much more common in children and young adults.
Surgery is important in the treatment of most sarcomas. Additional treatments, including chemotherapy and radiation therapy, may be administered before and/or after surgery. Chemotherapy significantly improves the prognosis for many sarcoma patients, especially those with bone sarcomas. Treatment can be a long and arduous process, lasting about a year for many patients.
Unfortunately, 25%-50% of patients treated with traditional therapies will develop metastatic disease. In the metastatic setting, complete responses to chemotherapy for sarcoma are rare and the median survival is 10-15 months. Building on the advancements made in other solid tumors, as well as a better understanding of cancer immunology, provides hope for the development of novel and effective immunotherapies in the treatment of sarcoma. Two antibody immunotherapies are approved for sarcoma patients, the RANK-targeting denosumab (Xgeva®) for bone sarcoma (osteosarcoma) and the PDGFR-targeting olaratumab for soft tissue sarcoma.
The role of the immune system in combatting cancer was first observed in sarcoma patients. Dating back to 1866, Wilhelm Busch in Germany observed tumor regressions in patients with sarcoma after postoperative wound infections. In the 1890s, William B. Coley at Memorial Hospital (now Memorial Sloan Kettering Cancer Center) also noticed a connection between bacterial infections and cancer regression and began to experiment with purposely inoculating cancer patients with bacteria in hopes of inducing infection and combatting cancer. Coley continued to experiment with his “toxin” therapy for the next 30 years, achieving lasting remissions in some cases. Though suggestive, the data generated by Coley were not consistent or reproducible in the hands of other researchers and, in 1963, the FDA ruled that the toxin therapy could no longer be used in the U.S. without first going through a new drug-approval process. It has not been approved to date.
Since 1977, CRI has given more than $2.6 million in support of sarcoma studies. Research by CRI investigators that are advancing the understanding and treatment of sarcoma include:
- In 2011, Steven A. Rosenberg, Mark Dudley (1993-1996 CRI postdoctoral fellow), and colleagues at the Surgery Branch of the National Cancer Institute demonstrated that adoptive immunotherapy with CD8+ T cells that were genetically engineered to recognize the NY-ESO-1 antigen could induce significant tumor regressions in patients with metastatic synovial sarcoma and melanoma. Their results were published in the Journal of Clinical Oncology.[i]
- CRI has partnered with Stand Up To Cancer (SU2C) to fund a “Dream Team” of researchers working to develop the next frontier of cancer immunotherapy. The group consists of several of the field’s preeminent scientists, including James Allison, Cassian Yee, Antoni Ribas, and Drew Pardoll. Several of the trials are now accruing patients and others are schedule to open later this year, including an adoptive cellular therapy plus immune checkpoint inhibitor trial for the treatment of NY-ESO-1+ sarcomas (synovial sarcoma and mixed round cell liposarcoma, which they recently demonstrated homogenously expresses NY-ESO-1). In this study, they are using NY-ESO-1-specific CD4+ T cells in combination with ipilimumab (NCT02210104).
- In 2012, using a sarcoma model, Robert D. Schreiber (CLIP grantee and Scientific Advisory Council member), Matthew Vesely (CRI graduate fellow), and their colleagues revealed a T cell-dependent mechanism of cancer immunoediting.[ii] Dr. Schreiber is noted for his studies with Lloyd J. Old that helped reestablish the theory of cancer immunosurveillance. In 2002, he, Old, and CRI postdoctoral fellow Hiroaki Ikeda coined the term immunoediting, and in 2004 Schreiber, Old, and CRI graduate fellow Gavin Dunn elaborated upon the model to describe three stages of cancer immunoediting—elimination, equilibrium, and escape (the “three Es of cancer immunoediting”)—to explain the dual roles of the immune system in promoting and suppressing cancer development. This model has since become widely adopted throughout the cancer research community.