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Immunotherapy for Sarcoma

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  • Sarcoma
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy Changing the Outlook for Patients with Sarcoma?

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.

History of Sarcoma Immunotherapy

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.

CRI Contributions and Impact

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.
Featured Patient

Every day I would feel my shoulder, and I could notice a difference. I could feel the tumor shrinking.

Donald Foley
Sarcoma  |  Diagnosed Age 13
Read My Story
Featured Scientist
Nina Bhardwaj, M.D., Ph.D.
Icahn School of Medicine at Mount Sinai
CLIP Investigator  |  2016
View Funding Profile

Sarcoma Statistics

1.7% Of all new cancer diagnoses in the US are Sarcoma
15% Of all childhood cancers are represented by sarcoma
6 Types of immunotherapy clinical trials

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Clinical Trials for Sarcoma

Current experimental immunotherapies for sarcoma fall into six broad categories: adoptive cell therapy, therapeutic cancer vaccines, checkpoint inhibitors/immune modulators, oncolytic virus therapy, adjuvant immunotherapies, and monoclonal antibodies.

  • Adoptive Cell Therapy
  • Therapeutic Vaccines
  • Checkpoint Inhibitors/Immune Modulators
  • Oncolytic Virus Therapies
  • Adjuvant Immunotherapies
  • Monoclonal Antibodies

A major avenue of immunotherapy for sarcoma is adoptive T cell therapy. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several clinical trials are currently under way:

  • A phase I study of T cells engineered to recognize the NY-ESO-1 marker (TBI-1301) in patients with solid tumors (NCT02366546). NY-ESO-1, a tumor-associated antigen, is not found on normal cells, with the exception of the testis.
  • A phase I trial to test genetically engineered NY-ESO-1 immune cells on child and adult patients with metastatic and recurrent synovial sarcoma (NCT01343043).
  • A phase I trial to test genetically engineered NY-ESO-1 immune cells, along with ipilimumab (Yervoy®), an anti-CTLA-4 antibody, on adult patients with metastatic synovial sarcoma or mixed round cell liposarcoma (NCT02210104) (not yet recruiting).
  • A phase I trial of chimeric antigen receptor (CAR) T cells genetically modified to express a protein receptor that recognizes GD2 and two costimulatory molecules for children and adult osteosarcoma patients (NCT01953900).
  • A phase I trial with CAR T cell therapy targeted to the GD2 protein is enrolling children and young adults with GD2+ cancers, including sarcoma, osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma (NCT00743496).
  • A phase I study of T cells engineered to recognize the NY-ESO-1, MAGE-A4, PRAME, survivin, and SSX markers in patients with solid tumors, including osteosarcoma, synovial sarcoma, and rhabdomyosarcoma (NCT02239861).


Therapeutic cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens.

  • A phase II trial of Vigil® (formerly FANG vaccine), which expresses an antigen and GM-CSF, for patients with metastatic Ewing sarcoma (NCT02511132).
  • A phase I trial of CMB305 in patients with locally advanced, relapsed, or metastatic cancer that expresses NY-ESO-1, including sarcoma (NCT02387125).
  • A phase I trial of DSP-7888, which targets the WT1 marker, for patients with select cancers, including sarcoma (NCT02498665).
  • A dendritic cell vaccine is in a phase I trial for adults and children with sarcoma (soft tissue and bone) (NCT01803152).


Another promising avenue of clinical research in sarcoma is the use of checkpoint inhibitors/immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash and/or enhance pre-existing anti-cancer immune responses.


  • A phase II trial of pembrolizumab (Keytruda®), an anti-PD-1 antibody, plus axitinib, which inhibits VEGF and PDGF, which help the tumors get nutrients (called angiogenesis), in patients with advanced alveolar soft part sarcoma and other soft tissue sarcoma (NCT02636725). There is also a phase II trial of pembrolizumab in patients with advanced non-resectable or metastatic sarcoma (NCT02406781), a phase I/II trial of pembrolizumab plus chemotherapy in patients with advanced cancer, including sarcoma (NCT02331251), and a phase I trial of pembrolizumab in patients with HIV and relapsed, refractory, or disseminated cancer, including Kaposi sarcoma (NCT02595866).
  • A phase II trial of atezolizumab (MPDL3280A), an anti-PD-L1 antibody, and CMB305, a vaccine, in patients with locally advanced, relapsed, or metastatic synovial or myxoid/round cell liposarcoma, whose tumors express the NY-ESO-1 protein (NCT02609984).
  • A phase I/II trial of nivolumab (Opdivo®), a PD-1 antibody, with or without ipilimumab (Yervoy®), a CTLA-4 antibody, in younger patients with recurrent or refractory sarcomas (NCT02304458). There is also a phase I trial of nivolumab, with or without ipilimumab, in patients with HIV-associated cancer, including Kaposi sarcoma (NCT02408861).
  • A phase I/II trial testing durvalumab (MEDI4736), which targets the PD-L1 pathway, and tremelimumab, an anti-CTLA-4 antibody, plus Poly-ICLC for patients with advanced, biopsy-accessible cancers, including sarcoma (NCT02643303). This trial is sponsored by Ludwig Cancer Research in partnership with the Cancer Research Institute.
  • A phase I trial testing PF-06801591, which targets the PD-1 marker, for patients with select cancers, including sarcoma (NCT02573259).


  • A phase I trial of TRX518 in patients with solid cancers (NCT01239134). This trial is sponsored by Ludwig Cancer Research in partnership with the Cancer Research Institute.


  • A phase I trial testing MGA271, a B7-H3 antibody, and ipilimumab, an anti-CTLA-4 antibody,  in patients with soft tissue sarcoma (NCT02381314), and a phase I study testing MGA217 and pembrolizumab in patients with refractory cancer, including soft tissue sarcoma (NCT02475213).
  • A phase I study to test MGD009, a B7-H3 x CD3 DART protein, in patients with unresectable or metastatic B7-H3-expressing cancer, including soft tissue sarcoma (NCT02628535).


Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.

  • A phase I/II trial of PexaVec (JX-594), a virus engineered to secrete GM-CSF and delete a kinase gene that is typically seen on cancer cells with a mutated RAS or p53 pathway, for patients with soft tissue sarcoma (NCT02630368).
  • A phase I/II trial to test talimogene laherparepvec (Imlygic™, T-VEC for short), a modified version of the herpes simplex virus I, the virus that causes cold sores, and radiation in patients with soft tissue sarcoma (NCT02453191).
  • A phase I trial of GL-ONC1, a vaccinia virus, for patients with solid cancers undergoing surgery (NCT02714374).


Adjuvants are substances that are either used alone or combined with other immunotherapies to boost the immune response. Some adjuvant immunotherapies use ligands—molecules that bind to proteins such as receptors—to help control the immune response. These ligands can be either stimulating (agonists) or blocking (antagonists).

  • A phase II trial of Poly-ICLC (Hiltonol®), a Toll-like receptor 3 agonist, for patients with select cancers, including sarcoma (NCT02423863).

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors.

  • Two phase II trials to test dinutuximab (Unituxin™), which targets GD2, a protein found on almost all neuroblastoma and osteosarcoma cells, in patients with recurrent osteosarcoma (NCT02502786NCT02484443).
  • A phase II trial to test denosumab (Xgeva®), which targets the RANK ligand, which is produced by bone cells and too much of it disrupts the natural balance of bone remodeling, in children with osteosarcoma (NCT02470091).

Go to our Clinical Trial Finder to find clinical trials of immunotherapies for sarcoma that are currently enrolling patients.


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American Cancer Society website, American Cancer Society Cancer Facts & Figures 2016, Sarcoma Foundation of America, Wikipedia,, CRI documents

Updated May 2016

[i] Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1; 29 (7): 917-24. (PMID: 21282551) (access the paper)

[ii] Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R, Magrini VJ, Arthur CD, White JM, Chen YS, Shea LK, Hundal J, Wendl MC, Demeter R, Wylie T, Allison JP, Smyth MJ, Old LJ, Mardis ER, Schreiber RD. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 2012 Feb 8; 482 (7385): 400-4. (PMID: 22318521) (access the paper)

*Immunotherapy results may vary from patient to patient.