Treating osteosarcoma with CAR T cells

Abstract

Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5-year survival as low as 5%-10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40 years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T-cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR-T treatment in a solid tumour. We will discuss the experiences with CAR-T therapy development and efficacy to combat the clinical challenges in OS.

miRNA-Based Feature Classifier Is Associated with Tumor Mutational Burden in Head and Neck Squamous Cell Carcinoma

“…Satisfactory results had been achieved in the immunotherapy for the treatment of aggressive or advanced cancers [ 32 – 34 ]. The progress of the tumor depends on the evasion of immune surveillance of cancer cells and the acquisition of effective immune response traits.…”

Sodium cantharidate targets STAT3 and abrogates EGFR inhibitor resistance in osteosarcoma

“…Previous studies revealed that EGFR gene copy number amplification and EGFR overexpression are common events in osteosarcoma, so targeting EGFR signaling is a promising therapeutic goal [21, 22]. Activation of EGFR stimulates several downstream signaling cascades, including the RAS/ RAF/MAPK, PI3K/Akt/mTOR, JAK/Src/STAT, and phospholipase C gamma/protein kinase C pathways, triggering oncogene transcription and promoting tumor proliferation, survival, invasion, and drug-resistance [23]. Available therapies targeting EGFR include monoclonal antibodies, e.g.…”

The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem

“…The main challenge of this immune approach is the identification of an optimal target expressed restrictively on tumor cells, in order to avoid toxicity and to selectively eradicate cancer cells. Up to now, few potential targets have been identified in OS [150]-the Human epidermal growth factor 2 (HER2), the Insulin-like Growth factor receptor-1 (IGFR1), and the tyrosine orphan-like receptor 1 (ROR1). HER-2 CAR-T cells have been shown to drive tumor regression in an animal model [151].…”