Lege Artis Medicinae

[Gene modified T cells against cancer]

SZÖŐR Árpád

OCTOBER 20, 2018

Lege Artis Medicinae - 2018;28(10)

[Chimeric antigen receptor modified (CAR) T cells are hailed as a revolutionary breakthrough in the field of oncology. CAR T cells were first applied, with outstanding success, in the treatment of various leukaemias, yielding unprecedented antitumor activity and long periods of disease free survival. Following the success of CAR T cell therapy in leukaemias, solid tumors should now be targeted. These are more complex targets, therefore CAR T cell therapy needs to be further optimized for this purpose. Also, some unfortunate side effects, including the potentially deadly global inflammation called cytokine storm have to be minimized and possibly even eradicated. The next decade will be an exciting time to define whether this therapy which is yet exclusively used for cancer patients is also successful in the treatment of other diseases. In a recent study, T cells reengineered with CAR derived chimeric autoantibody receptors (CAAR) efficiently prevented disease progression in pre-clinical animal models simulating the serious autoimmune disorder, pemphigus vulgaris. Therapy was based on CAAR constructs which have the unique ability to selectively recognize and eliminate the B-cell clones secreting autoantibodies against a self-protein, thus playing a key role in disease pathogenesis and progression. In this review, we would like to give an overview about the history of the CAR T-cell concept, summarize briefly the currently running clinical trials, and discuss the challenges and future prospects of CAR T-cell therapy.]

COMMENTS

0 comments

Further articles in this publication

Lege Artis Medicinae

[Does venous congestion decrease renal function - fiction or real?]

KOPITKÓ Csaba, MEDVE László, GONDOS Tibor

[Venous congestion can result in dysfunction of several organs. Although experimental data on renal dysfunction caused by venous congestion were already published about 90 years ago, those were difficult to extrapolate to humans, due to significant interracial differences. Acute pre-renal, or volume-sensitive kidney injury might respond to volume replacement; however, overt fluid resuscitation with or without right ventricular dysfunction can result in elevated central venous pressure. The glomerular capillary blood pressure, i. e. net filtration pressure in a single glomerulus is about 10 mmHg. Kidney dysfunction can both increase intra-abdominal pressure or elevate central venous pressure with or without decreased mean arterial pressure, can lead to renal dysfunction. In studies among patients with heart failure, or after cardiac or abdominal surgery, the increase of central venous pressure or intra-abdominal pressure above 8 mmHg resulted in impaired kidney function. This review summarizes both pre-clinical and clinical data on the role of intra-abdominal hypertension and venous congestion in the development of acute kidney injury.]

Lege Artis Medicinae

[On nursing in a different way - What are we talking about? ]

SÖVÉNYI Ferencné, PERKÓ Magdolna, FEDINECZNÉ Vittay Katalin

[Using an uncustomary approach to nursing history, authors review the intensive development process in the 1990s that resulted in the transition of nursing from an occupation to profession in Hungary. An occupa­tion attains professional status if its practitio­ners have access to education and training of a considerable duration, it has independent professional organisation, an ethical code of its own and is regulated by law. The article addresses these factors discussing at length the history and development of nurs­ing education and training in Hungary, subsequently it describes the process arching from practical nursing to the appearance of nursing science, an intrinsic part of which was the birth of a scientific nursing journal “Nővér”. The relevant and effective legislation on nursing and nursing practice is re­viewed comprehensively and the efforts to establish professional nursing organisations are described. It is maintained that framework conditions had to be established as a necessary precondition for nursing to professionalise itself on its own and become a vocation highly regarded by society. ]

Lege Artis Medicinae

[General questions and bioethical aspects of handling mistakes in health care]

KOVÁCS József

Lege Artis Medicinae

[The Painter’s Revolt against the Father, or Jesus Chastised ]

GEREVICH József

Lege Artis Medicinae

[Acetylsalicylic acid (ASA) 75 or 100 mg? ]

KIS János Tibor, ZSIGMOND Kálmán

[The acetylsalicylic acid (ASA) is one of the oldest and most widely used drugs in the world. Currently, it is the most commonly used for the treatment and prophylaxis of cardiovascular diseases. Today, there has been consensus that the risk of ASA’s side effects in primary prevention is greater than the expected benefits. However, it maintains its leading role in the secondary prevention of cardiovascular diseases. There is also a consensus that small doses are recommended for preventive purposes, but there is no agreement whether it should be 75 or 81 or 100 mg. The authors summa­rize the publications published in this topic. ]

All articles in the issue

Related contents

Clinical Oncology

[Gene modifi ed T cell therapy for patients with cancer]

HECZEY András

[T cells genetically modifi ed to express chimeric antigen receptors can combine the antigen specifi city of monoclonal antibodies with the cytotoxic function, active biodistribution and long term persistence of T cells. The approach can induce 90% complete remission rate in patients with CD19+ lymphoid leukemias; however, the in patients with solid tumors the antitumor effi cacy of CAR T cells have not reached similar levels yet. The increased levels of interleukin-6 due to T cell activation play key roles in the majority of side effects and using anti-IL-6 monoclonal antibody, tocilizumab can effectively treat these complications. Novel gene modifi cation strategies and improvements in CAR T cell manufacturing, the approach has the potential to fundamentally change the way patients with cancer are treated in the not too distant future.]

Clinical Neuroscience

[The role of sleep in the relational memory processes ]

CSÁBI Eszter, ZÁMBÓ Ágnes, PROKECZ Lídia

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]

Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report

OTTÓFFY Gábor, KOMÁROMY Hedvig

Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.