Chimeric antigen receptor (CAR) T cell therapy stands as a transformative advancement in immunotherapy, triumphing against hematological malignancies and, increasingly, autoimmune disorders. After a decade of relatively modest results for solid tumors, recent clinical trials and patient reports have also started to yield promising outcomes in glioblastoma and other challenging solid tumor entities. This Perspective seeks to explore the reasons behind these latest achievements and discusses how they can be sustained and expanded through different strategies involving CAR engineering and synthetic biology.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T cells are effectively used in certain hematological malignancies, though tumor relapse and limited success in solid tumors persist. Recent efforts focus on developing combination treatments to enhance outcomes and safety. Here, we provide a comprehensive overview of such combinatorial approaches and a consideration of ongoing clinical trials.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) represents a challenge in oncology, with limited treatment options for advanced-stage patients. Chimeric antigen receptor T cell (CAR T) therapy targeting mesothelin (MSLN) shows promise, but challenges such as the hostile immunosuppressive tumor microenvironment (TME) hinder its efficacy. This study explores the synergistic potential of combining proton radiation therapy (RT) with MSLN-targeting CAR T therapy in a syngeneic PDAC model.
View Article and Find Full Text PDFAs a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group.
View Article and Find Full Text PDFMultidrug resistance (MDR) causes difficulties in the treatment of infections and cancer. Research and development studies have become increasingly important for the strategy of preventing MDR. There is a need for new multitarget drug research and advancement to reduce the development of drug resistance in drug-drug interactions and reduce cost and toxic effects.
View Article and Find Full Text PDFCancer Immunol Res
July 2023
In this issue, Tsimberidou and colleagues report the results of a first-in-human clinical trial using a personalized, multi-target, endogenous T-cell therapy in patients with metastatic solid tumors. This, and results of other recently published clinical trials, confirms the rationale of multi-target approaches that can increase tumor responses and counteract tumor heterogeneity and mechanisms of immune evasion. See related article by Tsimberidou et al.
View Article and Find Full Text PDFSchiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties.
View Article and Find Full Text PDFIncomplete surgery of solid tumors is a risk factor for primary treatment failure. Here, we have investigated whether chimeric antigen receptor T cells (CARTs) could be used as an adjuvant therapy to clear residual cancer cells. We tested the feasibility of this approach in two partial resection xenograft models using mesothelin-specific CARTs.
View Article and Find Full Text PDFPurpose: Demodex folliculorum and Demodex brevis are common ectoparasites on skin that also can lead to blepharitis and chalazion. The aim of our study is to determine the prevalence of Demodex spp. in eyelashes of patients diagnosed with chronic blepharitis and chalazion.
View Article and Find Full Text PDFTurkiye Parazitol Derg
September 2022
Objective: This study was conducted to determine the period prevalence of hydatid cysts isolated from the livers of cattle slaughtered at a slaughterhouse in Konya.
Methods: For this purpose, 49,545 cattle were slaughtered and examined for the presence of hydatid cysts in the liver. The study was conducted between June 01, 2018, and May 31, 2019.
Clonal hematopoiesis of indeterminate potential (CHIP) is common in patients with hematologic malignancies. Recent publications provide evidence that CHIP may affect chimeric antigen receptor T-cell therapy efficacy and that the incidence of treatment-related toxicities such as cytokine release syndrome and immune effector-cell associated neurotoxicity syndrome may be affected. See related article by Saini et al.
View Article and Find Full Text PDFCD19- and B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells have enabled unprecedented responses in a subset of refractory patients with B-cell and plasma cell malignancies, leading to their approval by the FDA for the treatment of leukemia, lymphoma, and myeloma. These "living drugs" can become part of a synthetic immune system, persisting at least a decade in some patients. However, despite this tremendous impact, significant unmet treatment needs remain for patients with hematologic malignancies and solid cancers.
View Article and Find Full Text PDFObjective: This study aimed to determine the prevalence of liver hydatidosis in sheep slaughtered in a private slaughterhouse in Konya and to estimate the economic loss incurred because of the disease.
Methods: The study was conducted over a period of 12 months between 1 June 2018 and 31 May 2019. Given that the aim of this investigation was to determine the prevalence of liver hydatidosis, only the livers of 41,002 sheep were examined for hydatid cysts.
Whereas approximately half of metastatic melanoma patients benefit from combined immune checkpoint inhibition targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1), for those who do not respond, further strategies and treatment options need to be developed. Thus, focus is turning to the use of chimeric antigen receptor (CAR) T cells, a novel therapy that has not yet achieved a major breakthrough in solid tumors despite the impressive response rates reported for their use in hematologic malignancies. In melanoma and other solid tumor entities, different problems still need to be addressed to improve this therapy, with mechanisms to counteract tumor escape being one of them.
View Article and Find Full Text PDFAfter the recent success and approvals of chimeric antigen receptor (CAR) T cells in haematological malignancies, its efficacy is currently evaluated in a broad spectrum of tumor entities including melanoma. However, severe and potentially life-threatening side effects like cytokine release syndrome, neurologic toxicities, and the competing risk of morbidity and mortality from the treatment itself are still a major limiting factor in the current CAR T-cell landscape. In addition, especially in solid tumors, the lack of ideal target antigens to avoid on-target/off-tumor toxicities also restricts its use.
View Article and Find Full Text PDFBackground: The approvals of immune checkpoint inhibitors for several cancer types and the rapidly growing recognition that T cell-based immunotherapy significantly improves outcomes for cancer patients led to a re-emergence of cancer vaccines, including dendritic cell (DC)-based immunotherapy. Blood and tissue biomarkers to identify responders and long-term survivors and to optimize cost and cost-effectiveness of treatment are greatly needed. We wanted to investigate whether blood eosinophilia is a predictive biomarker for patients with solid tumors receiving vaccinations with DCs loaded with autologous tumor-RNA.
View Article and Find Full Text PDFBackground: Although dendritic cell (DC)-based cancer vaccines represent a promising treatment strategy, its exploration in the clinic is hampered due to the need for Good Manufacturing Practice (GMP) facilities and associated trained staff for the generation of large numbers of DCs. The Quantum bioreactor system offered by Terumo BCT represents a hollow-fiber platform integrating GMP-compliant manufacturing steps in a closed system for automated cultivation of cellular products. In the respective established protocols, the hollow fibers are coated with fibronectin and trypsin is used to harvest the final cell product, which in the case of DCs allows processing of only one tenth of an apheresis product.
View Article and Find Full Text PDFImmune checkpoint blockade with anti-PD-1 antibodies is showing great promise for patients with metastatic melanoma and other malignancies, but despite good responses by some patients who achieve partial or complete regression, many others still do not respond. Here, we sought peripheral blood T-cell biomarker candidates predicting treatment outcome in 75 stage IV melanoma patients treated with anti-PD-1 antibodies. We investigated associations with clinical response, progression-free survival (PFS) and overall survival (OS).
View Article and Find Full Text PDFBackground: Spindle cell oncocytoma (SCO) is a rare non-neuroendocrine neoplasm of the pituitary gland. In general, surgical excision and radiation therapy is performed. However, local recurrences are frequently seen, requiring repeated surgical and radio-oncological interventions.
View Article and Find Full Text PDFIntroduction of a tumor antigen-specific T cell receptor (TCR) into patient-derived lymphocytes has already exhibited promising results for the treatment of melanoma and other malignancies in clinical trials. However, insufficient or unsuccessful ex vivo manufacturing of engineered T cells due to low expansion and/or transduction rate can still be observed in some patients. Thus, we isolated human CD8 T cells from healthy donors and equipped them with a gp100-specific TCR using a lentiviral construct in combination with a novel chemical lentiviral transduction enhancer (Lentiboost) to increase the rate of transduced cells.
View Article and Find Full Text PDFActa Derm Venereol
September 2019
Mycobacterium chelonae is a rapidly growing non-tuberculous mycobacterium, which causes infections of the human skin and soft tissue. Despite an increasing incidence of such infections, patients are often misdiagnosed. We report here 5 patients with cutaneous and/or soft tissue infection due to M.
View Article and Find Full Text PDFBackground: Sentinel lymph node status is a strong prognostic factor in melanoma. However, up to 21% of sentinel lymph node-negative patients develop locoregional and distant metastases during follow-up.
Aim: To analyze risk factors for locoregional and distant metastasis in patients with sentinel lymph node-negative melanoma.