Abstract
Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and post-operative chemotherapy. In order to ameliorate survival rates of patients, new therapeutic approaches have been evaluated, mainly immunotherapy with antibody-drug conjugates or immunoconjugates. These molecules consist of a carrier (frequently an antibody) joined by a linker to a toxic moiety (drug, radionuclide, or toxin). Although several clinical trials with immunoconjugates have been conducted, mainly in hematological tumors, their potential as therapeutic agents is relatively under-explored in many types of cancer. In this review, we report the immunoconjugates directed against OS surface antigens, considering the in vitro and in vivo studies. To date, several attempts have been made in preclinical settings, reporting encouraging results and demonstrating the validity of the idea. The clinical experience with glembatumumab vedotin may provide new insights into the real efficacy of antibody-drug conjugates for OS therapy, possibly giving more information about patient selection. Moreover, new opportunities could arise from the ongoing clinical trials in OS patients with unconjugated antibodies that could represent future candidates as carrier moieties of immunoconjugates.
Highlights
Bone sarcomas are a group of rare malignant tumors that can arise from bone tissue, cartilage, and muscle, accounting for about 0.2% of all human neoplasms [1]
These molecules consist of a carrier part, frequently a monoclonal antibody, whose function is to deliver a toxic moiety to specific tumor targets
Several immunoconjugates directed against certain OS surface targets have been explored in vitro and in vivo (Table 1)
Summary
Bone sarcomas are a group of rare malignant tumors that can arise from bone tissue, cartilage, and muscle, accounting for about 0.2% of all human neoplasms [1]. Osteosarcoma (OS) is the most common primary bone malignancy. It is an aggressive osteoid-producing tumor of mesenchymal origin, characterized by a complex and, frequently, uncertain etiology. Occurring during the adolescent growth spurt, with a peak in the second decade of life and a higher incidence in males, OS shows a bimodal distribution with a second peak in the population over 65 years old, frequently associated with prior radiation therapy or Paget’s disease [5]. Patients with metastatic disease or recurrence, who suffer a worse prognosis, need new therapeutic approaches, in order to go beyond the above reported rates of survival
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