Targeting the immune-privileged myofibroblast in oral submucous fibrosis by CAR T-cell therapy.

• Oral submucous fibrosis (OSMF) is a fibrotic disease associated with myofibroblasts driven fibrosis. • Fibroblast activating factor (FAP) is expressed on such activated myofibroblasts. • Adoptive transfer of T cells that express a chimeric antigen receptor against FAP is proposed as a targeted immunotherapy for OSMF. • This therapy will reduce the fibrosis and down-regulate the myofibroblasts associated with malignant transformation events. Despite several advancements in understanding the pathogenesis of oral submucous fibrosis (OSMF), there is no definitive therapy for the complete remission of the disease process. This is attributed to the fact that any chronic fibrotic disease targeting myofibroblasts, the primary cells responsible for fibrosis is challenging. The betel quid-associated chemicals, predominantly, arecoline and arecaidine, advance the activation of resident fibroblasts to myofibroblasts in OSMF, resulting in uncontrolled and excessive production of collagen. The myofibroblasts, which are associated with the malignant transformation express fibroblast-activating protein (FAP) on their surface that could be selectively targeted for the treatment of OSMF. In the present paper, we propose that the adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein (FAP CAR T cell therapy) results in a significant reduction in fibrosis and restoration of function in OSMF. The detailed procedural aspects of this therapy along with experimental designs are also discussed. Since myofibroblasts are involved in the malignant transformation of OSMF, the selective elimination of these cells will reduce the cancer development and ultimately the cancer burden. [ABSTRACT FROM AUTHOR]