CAR-Based Approaches to Cutaneous T-Cell Lymphoma

Conclusions The major challenges in the development of adoptive cell therapy for T cell tumors, as mentioned above, remain fratricide, T cell aplasia and the potential for leukemic transduction or poor T cell function if used in the autologous setting. Approaches to overcome fratricide include the genetic modification and deletion of the T cell antigen in the case of long-term CAR-T cell persistence or regulated CAR-T expression. To ensure restoration of T cell immunity, transient CAR expression can be achieved incorporation of a CAR suicide gene, transient CAR expression using mRNA electroporation, or short-lived NK cell lines. Finally, given that these toxicities may be tolerable initially, CAR-T cells followed by an ablative hematopoietic stem cell transplant may allow for hematologic rescue following CAR-T mediated disease clearance. As most of the models to date have utilized normal donor human T cells for CAR manufacturing, we must also consider the underlying fitness of the starting cell product. Peripheral T-cells from patients with underlying T cell malignancy routinely demonstrate impairments in T cell function as well as reduced quantities in peripheral blood, given the extensive prior treatment burden and immune-dysregulation. Approaches utilizing allogeneic donors and gene-editing techniques to remove the endogenous TCR, or CAR products generated from autologous or allogeneic NK cells may offer creative solutions. These include the potential for multiple allogen...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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Authors: Montazeri K, Bellmunt J Abstract Introduction: Since the approval of immune checkpoint inhibitors (ICIs), there has been continuing and significant progress in urothelial cancer (UC) treatment. However, only about one fifth of UC patients respond to ICI. Recently, erdafitinib was developed for treating locally advanced or metastatic UC (mUC) with FGFR3 or FGFR2 alterations, accounting for 15-20% of patients. Erdafitinib is the first targeted therapy ever approved for mUC.Areas covered: This review summarizes the preclinical and clinical data on erdafitinib for UC. PubMed search and relevant articles presen...
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
Authors: Jakubowska K, Koda M, Kisielewski W, Kańczuga-Koda L, Famulski W Abstract The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study ...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
The objective of the present study was to evaluate the beneficial effect of endorectal power Doppler/grayscale ultrasound-guided biopsy over that of mpMRI/TRUS-guided biopsy for decision-making regarding prostatectomy in males with a high risk of prostate cancer. Data regarding endorectal power Doppler/grayscale ultrasound-guided biopsies and mpMRI/TRUS-guided biopsies of 1,094 males with elevated specific prostate antigen, were included. Radical prostatectomy was performed in males aged
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Zhang H, Wang Y, Yang G, Yu H, Zhou Z, Tang M Abstract Cartilage injury is difficult to repair since the cartilage tissue lacks self-restoration ability. Improved formation of chondrocytes differentiated from the mesenchymal stem cells (MSC) by genetic regulation is a potentially promising therapeutic option. SOX9 is a critical transcription factor for mesenchymal condensation prior to chondrogenesis. Previous studies demonstrated that several microRNAs (miRNAs or miRs) play a critical role in the chondrogenic differentiation of MSCs. However, the interactional relations between miR-30a and SOX9 during cho...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Toma M, Beluşică L, Stavarachi M, Apostol P, Spandole S, Radu I, Cimponeriu D Abstract Colorectal cancer (CRC) is a disease preventable in up to 50% of the patients by lifestyle modifications. The preventive strategy for the decrease in the incidence and mortality of CRC is based on understanding the relations between the environmental and genetic factors. The most important identified risk factors for CRC are aging, personal and familial history of CRC or adenomas, hereditary colon cancer syndromes, dietary patterns, and inflammatory bowel disease. The purpose of this review is to update data referring ...
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
This article reviews some epidemiological, clinical, diagnostic and therapeutic aspects of these conditions. PMID: 31803301 [PubMed]
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Conclusions &discussion: This paper is designed as a guideline and instruction manual to help those with less experience through particular situations in surgical burn care. Early excision and immediate coverage of the burn wounds represent nowadays the standard care for extensive burned patients. For patients with massive thermal injury, temporary coverage with allografts is essential. The use of allograft has multiple benefits because it plays both as physiologic and mechanical barriers. PMID: 31803300 [PubMed]
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Conclusions: CD200 has a great impact in diagnosing B- chronic lymphoproliferative disorders, especially when we want to determine the origin of a CD19, CD5 positive population and distinguish between CLL and MCL. CD 23 is a reliable marker in those cases, but, as we showed, CD23 might have a lower specificity than CD200 for CLL. We added CD200 in our panels in order to diagnose chronic lymphoproliferative disorders, not to replace CD 23, but to improve and save time in our diagnostic process. The high expression of CD200 in CLL and HCL could open the option for new- targeted therapy (anti-CD200). PMID: 31803290 [PubMed]
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Authors: Ivanescu AM, Oprea M, Momanu R, Coles E, Colita A, Lupu AR Abstract Chronic lymphocytic leukemia is still one of the most common hematologic malignancies. Finding a curative solution is the objective of numerous followed cases and clinical trials. Diagnosis is based on the interlocking of classic elements and newly identified prognostic factors but time to first treatment is still an open issue. CD38, ZAP 70, IgHV gene mutational status and cytogenetic changes are proven negatively influence the evolution of chronic lymphocytic leukemia. Whether through aggressive rapid evolution or by the difficulty of ob...
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Authors: Oprea MM, Ivanescu AM, Colita A, Coles E, Momanu RC, Berbec N, Lupu AR Abstract Biological complexity of mechanisms of autoimmune hemolytic anemia (AHAI) in chronic lymphocytic leukemia B (CLL) and the relation cause / effect between these two diseases has been extensively researched, but currently is still far from being completely understood. It is known that the immune system has an important role in the pathogenesis of autoimmune diseases but also in the chronic lymphoproliferative malignancies. In this process of autoimmunity associated with immunodeficiency, the CLL neoplastic cells, the non-malignan...
Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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