Arthroscopic bone graft procedure combined with arthroscopic subscapularis augmentation (ASA) for recurrent anterior instability with glenoid bone defect: a cadaver study

Abstract Background Glenoid bone loss and capsular deficiency represent critical points of arthroscopic Bankart repair failures. The purpose of this study was to evaluate an all-arthroscopic bone block procedure associated with arthroscopic subscapularis augmentation (ASA) for treating gleno-humeral instability with glenoid bone loss (GBL) and anterior capsulo-labral deficiency. Our hypothesis was that these two procedures could be combined arthroscopically. The feasibility of this technique and its reproducibility, and potential neurovascular complications were evaluated. Methods A tricortical bone graft was harvested from the cadaveric clavicle, and in one case a Xenograft was used. An anterior-inferior GBL of about 25% was created. Two glenoid tunnels were set up from the posterior to the anterior side using a dedicated bone block guide, and four buttons were used to fix the graft to the glenoid. The subscapularis tenodesis was performed using a suture tape anchor. Afterwards, the shoulder was dissected to study the relationship between all portals and nerves. The size of the bone block, its position on the glenoid and the relationship with the subscapularis tendon were investigated. Results In all seven specimens (five left and two right shoulders), the bone block was flush with the cartilage and fixed to the anterior-inferior part of the glenoid. No lesions of the surrounding neurovascular structures were observed. No interference was found between the two bone block tunnels and the anchor tunnel used for the tenodesis. Conclusions This study demonstrated the feasibility and reproducibility of this combined arthroscopic technique (bone block associated with ASA) in the treatment of anterior shoulder instability associated with anterior bone loss and anterior capsular deficiency

Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma

5T4 (trophoblast glycoprotein, TPBG) is a transmembrane tumor antigen expressed on more than 90% of primary renal cell carcinomas (RCC) and a wide range of human carcinomas but not on most somatic adult tissues. The favorable expression pattern has encouraged the development and clinical testing of 5T4-targeted antibody and vaccine therapies. 5T4 also represents a compelling and unexplored target for T-cell receptor (TCR)-engineered T-cell therapy. Our group has previously isolated high-avidity CD8 + T-cell clones specific for an HLA-A2-restricted 5T4 epitope (residues 17–25; 5T4 p17 ). In this report, targeted single-cell RNA sequencing was performed on 5T4 p17 -specific T-cell clones to sequence the highly variable complementarity-determining region 3 ( CDR3 ) of T-cell receptor α chain ( TRA ) and β chain ( TRB ) genes. Full-length TRA and TRB sequences were cloned into lentiviral vectors and transduced into CD8 + T-cells from healthy donors. Redirected effector T-cell function against 5T4 p17 was measured by cytotoxicity and cytokine release assays. Seven unique TRA - TRB pairs were identified. All seven TCRs exhibited high expression on CD8 + T-cells with transduction efficiencies from 59 to 89%. TCR-transduced CD8 + T-cells demonstrated redirected cytotoxicity and cytokine release in response to 5T4 p17 on target-cells and killed 5T4 + /HLA-A2 + kidney-, breast-, and colorectal-tumor cell lines as well as primary RCC tumor cells in vitro. TCR-transduced CD8 + T-cells also detected presentation of 5T4 p17 in TAP1/2 -deficient T2 target-cells. TCR-transduced T-cells redirected to recognize the 5T4 p17 epitope from a broadly shared tumor antigen are of interest for future testing as a cellular immunotherapy strategy for HLA-A2 + subjects with 5T4 + tumors