ABSTRACT
Chimeric antigen receptors (CARs) have found clinical success in B cell malignancies, but a dearth of potential targets limits their wider clinical application, especially in solid tumours. Here, we describe the development of an anti-annexin A2 CAR, CAR(2448), derived from an antibody found to have activity against epithelial ovarian cancer cell lines. The spacer length of CAR(2448) was optimised based on in vitro cytotoxic activity against ovarian cancer (OC) cell lines via a real-time cytotoxicity assay. The longer spacer CAR(2448)L T cells exhibit significant effector activity, inducing inflammatory cytokine release and cytotoxicity against OC cell lines. Furthermore, CAR(2448)L-BBz T cells induced enhanced survival in an in vivo OC xenograft model and reduced tumour volume by 76.6%. Our preclinical studies of CAR(2448) suggest its potential for the unmet need of novel strategies for the treatment of ovarian cancer.
Subject(s)
Annexin A2/immunology , Carcinoma, Ovarian Epithelial/therapy , Immunotherapy, Adoptive , Ovarian Neoplasms/therapy , Receptors, Chimeric Antigen/therapeutic use , Animals , Annexin A2/antagonists & inhibitors , Carcinoma, Ovarian Epithelial/immunology , Cell Line, Tumor , Female , Humans , Immunotherapy, Adoptive/methods , Mice, Inbred NOD , Mice, SCID , Ovarian Neoplasms/immunology , Receptors, Chimeric Antigen/immunology , T-Lymphocytes/immunology , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: Craniofacial fibrous dysplasia is a benign slowly progressive disease in which normal craniofacial bones are replaced by immature fibro-osseous tissue. Orbital involvement may present as visual loss in some patients. The etiology of visual loss in orbital fibrous dysplasia is still unclear, with many theories proposed in recent literature. This has led to developments in the controversy regarding the role of prophylactic optic nerve decompression in asymptomatic orbital fibrous dysplasia patients. This case report and literature review evaluates the need for early surgical intervention in such patients, as well as highlights other aspects of the condition and its management. DESIGN: Case report and literature review. METHODS: This was a case report of a 12-year-old Chinese girl who developed progressive visual loss in association with craniofacial fibrous dysplasia involving the orbit. Literature regarding the epidemiology, pathophysiology, clinical features, diagnosis, investigations, and management was searched from the PubMed database. RESULTS: Extradural decompression of the optic nerve resulted in marked visual improvement, with temporal optic atrophy noted postoperatively. Literature review revealed a number of recent studies recommending against prophylactic optic nerve decompression, but early surgical intervention upon onset of visual loss is suggested. CONCLUSIONS: Immediate surgical referral and early optic nerve decompression is recommended upon onset of visual loss. Periodic follow-up is recommended to monitor for recurrence and malignant transformation.
