Immunotherapy for Bone and Soft Tissue Sarcomas.

Takenori Uehara,Toshifumi Ozaki,Ken Takeda,Tomohiro Fujiwara,Heiichiro Udono,Toshiyuki Kunisada

doi:10.1155/2015/820813

Abstract

Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

Highlights

Sarcomas are malignant tumors of mesenchymal origin, including bones, muscles, fat, nerves, and blood vessels
Conventional treatment for bone and soft tissue sarcomas consists of surgical resection, chemotherapy, and radiotherapy
Cytokine therapies were initially regarded as a form of immunotherapy; their effectiveness was limited because of their toxicities

Summary

Introduction

Sarcomas are malignant tumors of mesenchymal origin, including bones, muscles, fat, nerves, and blood vessels. Based on the survival data obtained from the National Cancer Data Base of the American College of Surgeons, the relative 5year survival rate is approximately 66% for patients with bone and soft tissue sarcomas, 53.9% for osteosarcomas (n = 8,104), 75.2% for chondrosarcoma (n = 6,476), and 50.6% for Ewing’s sarcomas (n = 3,225) [3]. Standard treatment modalities include surgical resection, chemotherapy, and often radiotherapy [6,7,8] Despite these multimodality therapies, survival rates have not been improved over recent 20 years [9]. The sarcoma completely regressed after a severe episode of erysipelas. Utilizing modern cancer immunotherapies for patients with sarcomas began in the 1980s as a cytokine therapy [32, 33], and more recently antigen-specific cancer vaccines and/or cell therapies have been developed [34, 35]

Overview of Cancer Immunology

Outcomes of Clinical Trials for Bone and Soft Tissue Sarcomas

Findings

Conclusion and Future Directions