Overcoming barriers of car T-cell therapy in patients with mesothelin-expressing cancers.

One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors.

Possible Compartmental Cytokine Release Syndrome in a Patient With Recurrent Ovarian Cancer After Treatment With Mesothelin-targeted CAR-T Cells.

Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies. A 52-year-old woman with BRCA 1 mutation positive heavily pretreated advanced recurrent serous ovarian cancer was treated under a compassionate use protocol with autologous mesothelin-redirected chimeric antigen receptor T cells (CART-meso). Autologous T cells were transduced to express a receptor composed of an extracellular antimesothelin single-chain variable fragment fused to 4-1BB and TCR-zeta signaling domain.

Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy.

B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets.

Race-based disparities in loss of functional independence after hysterectomy for uterine cancer.

Purpose: Racial disparities in uterine cancer-related outcomes have been reported. The goal of this study was to determine if race, pre-operative body mass index (BMI), and medical comorbidities are predictors of loss of functional independence after hysterectomy for uterine cancer.

Methods: Loss of independence was defined as a change from pre-operative functional independence, to a post-operative requirement of discharge to a post-care facility, or death within the first 30 days following uterine cancer surgery.

Mesothelin as a target for chimeric antigen receptor-modified T cells as anticancer therapy.

Mesothelin is a promising target for immune-based therapy, specifically for mesothelioma and pancreatic and ovarian cancers that have high levels of mesothelin expression. Many preclinical and clinical studies that target tumors with high mesothelin expression with antibodies, immunotoxins, antibody-drug conjugates and vaccines have shown the potential of mesothelin as a target. Studies of T cells genetically modified with chimeric antigen receptors (CAR) report significant efficacy in hematologic malignancies, and antimesothelin CAR T cells are currently being investigated in clinical studies.