Paving the way towards universal treatment with allogenic T cells
AbstractWith several different CAR T cell therapies under advanced phases of clinical trials, and the first FDA-approved CAR treatments in 2017 (Yescarta and Kymriah), CAR T cell therapy has become one of the most promising therapies for the treatment of certain types of cancer. This success has bred an opportunity to optimize the production of CAR T cells for easier patient access. CAR T cell therapy is a rather expensive and personalized process that requires expensive measures to collect cells from patients, engineer those cells, and re-infuse the cells into the patient with adequate quality controls at each phase. With this in mind, significant attempts at creating a “universal” CAR T cell are underway in order to create an “off-the-shelf” product that would reduce the expense and time required for traditional CAR T cell treatment. The primary obstacle facing this endeavor is avoiding graft-versus-host disease that accompanies allogeneic transplants betw een genetically dissimilar individuals. With the advent of CRISPR and TALEN technology, editing the genome of allogeneic cells has become very possible, and several groups have provided initial data analyzing the effects of CAR T cells that have been edited to avoid host rejection and avoid endogeno us TCR alloreactivity. These engineered cells not only have to avoid GVHD but also have to retain their anti-tumor efficacy in vivo. Here, we expand on the recent efforts and strides that have been made...
Carbohydrate antigen 125 (CA125), a marker for ovarian cancer, is thought to be associated with the clinical severity of heart failure (HF) and fluid congestion. Mesothelial cells in the pericardium, pleura, peritoneum and M ¨ullerian epithelium produce CA125 presumably in response to mechanical (congestion) stress. With the growing use of left ventricular assist device (LVAD) for advanced HF, assessment of right ventricular (RV) function and hemodynamics is of major interest. We aimed to assess CA125 as a predictor of right heart function and hemodynamics.
African Americans (AA) have worse survival compared to Caucasians after heart transplantation (HTx). We assessed whether AA are at higher risk of acute cellular rejection (ACR), graft failure (GF) and cancer when compared to Caucasians and Other races in the modern era.
Gene expression profile (GEP) monitoring by AlloMap ® is ISHLT-guideline recommended for graft surveillance after heart transplant (HT). The Outcomes in AlloMap Registry (OAR) is an observational, prospective study of HT patients monitored by AlloMap. The effect of malignancy on AlloMap scores is not well characterized. The large cohort of OAR patie nts with clinical data associated with AlloMap scores permits this characterization.
Polyfunctional T cells (PTC) have the ability to secrete ≥2 cytokines per cell when stimulated and increased presence of PTC is associated with favorable outcomes in patients undergoing chimeric antigen receptor (CAR) T cell therapy for cancer. In pediatric heart transplant recipients (PHT), the development of PTC may represent increased exposure to don or specific antigens with the potential to induce greater allograft damage through elevated cytokine production; however, the ability of circulating PTC to predict acute cellular rejection (ACR) in PHT is unknown.
We aimed to examine the effectiveness of serial follow-up phone calls as an intervention after clinic visits to enhance compliance with cancer surveillance among heart transplant (HT) patients.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Recent reports indicate risk for fulminant myocarditis in non-transplant patients and severe, potentially fatal rejection in transplant recipients treated with ICIs. As the use of ICIs is expanding, there is an imperative to address gaps in our understanding of risk for ICI use in the post-transplant patient. The aim of this submission is to highlight a case series of thoracic transplant patients treated with ICIs and to introduce a clinical registry of ICI use.
This study was undertaken to identify risk factors using the UNOS database.
There are over 15 million Cancer Survivors (CSr) in the United States and this number is estimated to increase further with improvement in cancer therapeutics and an aging population. In previous studies, CSr undergoing Left Ventricular Assist Device (LVAD) implantation were found to have worse outcomes than patients without a history of cancer. The aim of this study was to ascertain the effect of a previous history of cancer on adverse events and survival in patients undergoing HeartMate 3(HM3) implantation.
We present a series of 104 heart transplants performed for any cancer involving the heart from 1982 to 2017 from the International Society of Heart and Lung Transplant (ISHLT) Thoracic Organ Transplant Registry.
Abstract Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. In the treatment of cSCC, it is necessary to remove it completely, and reconstructive surgery, such as a skin graft or a local or free flap, will be required, depending on the size, with donor-site morbidity posing a burden to the patient. The high hydrostatic pressure (HHP) technique has been developed as a physical method of decellularizing various tissues. We previously reported that HHP at 200 MPa for 10 min could inactivate all cells in the giant congenital melanocytic nevus, and we have already started a c...