Clinical Oncology

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


FEBRUARY 10, 2017

Clinical Oncology - 2017;4(01)

[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.]



Further articles in this publication

Clinical Oncology

[The role of PET in clinical oncology]


[Positron emission tomography (PET) has earned an important role in clinical imaging, where it is used almost exclusively as hybrid modality such as PET/CT and PET/MR. The driving force behind the development of the method and the increasing clinical penetration of PET in the past two decades was clearly its use in Oncology. The most used tracer in PET is the 18 F-labeled fl uoro-deoxy-glucose (FDG). With the help of this molecule malignant tumors and their metastases, in which anaerobic glycolysis is typically increased, can be identifi ed with high sensitivity in the total body volume. However, FDG is not a tumor specifi c tracer, thus both false positivity and false negativity may occure which reduces the diagnostic accuracy. Indications of FDG PET studies in Oncology continuously evolved, owing to scientifi c publications, large scale national programs and even health-economic considerations. This publication describes the well-established indications of FDG PET/CT(MR) tests in cancer diagnostics and furthermore discusses more recent new PET tracers already being applied as well as those expected to be used in the future.]

Clinical Oncology


A szerkesztők

Clinical Oncology

[Treatment of neuroendocrine tumors]


[Recently, the therapeutic possibilities for the locally invasive or metastatic neuroendocrine tumors developed signifi cantly, although we have no widely accepted predictive or prognostic factors, which could help to design the most effective sequential therapy. To make therapeutic strategy the internationally accepted clinical guidelines should be considered. The therapeutic activity has to be performed in oncological centers with the support of a multidisciplinary team.]

Clinical Oncology

[Diffuse large B-cell lymphoma – a road to personal therapy]


[The majority of patients with diffuse large B-cell lymphoma can be cured using the standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) based therapy. However, approximately 30-40% of the patients are refractory to the therapy or they relapse. The currently available salvage therapies represent a realistic curative approach only for approximately one quarter of the patients. Therefore, there is unmet clinical need for more effi cient fi rst line and salvage therapies in DLBCL. The rapid advances in the fi eld of molecular genetic techniques lead to a better understanding of the biological heterogeneity as well as the discovery of the key factors involved in the pathogenesis of the disease. Nowadays, the distinction between the cases with germinal center B-cell and activated B-cell origin characterized with different prognosis has therapeutic implications. Presently, the therapy of the so-called double-hit lymphomas also represents an unmet clinical need. The next generation sequencing based studies lead to the discovery of novel molecular targets, including components of different cellular signaling pathways, immune checkpoints and components of the microenvironment. Targeted therapies against many of these molecular targets are being tested in different clinical trials. Due the heterogeneity of the disease, it is of critical importance to identify those patient groups who will benefi t from a particular targeted therapy. Hopefully, this risk-adopted therapeutic approach will become soon available for patients with DLBCL. Currently, the R-CHOP therapy still represents the gold standard in treatment of patients with DLBCL.]

Clinical Oncology

[Cancer treatment induced gastrointestinal complications]

AL-FARHAT Yousuf, AUTH Péter

[Systemic therapy (ST) (including chemotherapy, targeted therapy, and immunotherapy) or radiation therapy (RT) can induce gastrointestinal side effects, which frequently affect patient’s quality of life. Sometimes side effects could be dose-limiting, or a reason to stop the treatment. The incidence and severity of gastrointestinal complications in patient’s receiving ST, RT, or chemoradiotherapy are affected by numerous factors, including: therapeutic agents, doses and route of administration, target of the RT (upper, lower abdomen or body) and individual patient variability (age, sex, prior cancer therapy, comorbidities, performance status). Mucositis occurs in approximately 20% to 40% of patients receiving conventional chemotherapy, 80% of patients receiving high-dose chemotherapy, nearly all patients receiving head and neck radiation therapy. mTOR inhibitor-associated stomatitis (mIAS) is the most frequent dose-limiting toxicity (52.5%). More than 90% of patients receiving highly emetogenic chemotherapy will have episodes of vomiting. However, only about 30% of these patients will vomit if they receive prophylactic antiemetic regimens.]

All articles in the issue

Related contents

Clinical Oncology

[Treatment of mesothelioma - an update]

MOLDVAY Judit, HEGEDŰS Balázs, KOVÁCS Ildikó, DÖME Balázs

[Malignant pleural mesothelioma is an aggressive tumor arising from the mesothelial cells lining the pleura. It is an asbestos related disease with increasing incidence both in Europe and in Hungary. This often fatal disease is characterized by rapid progression, and unfortunately, treatment options are very limited to date. Thus every effort should be made to better understand the pathological and molecular biological characteristics of this disease in order to develop new treatment strategies. This summary reviews the treatment options available today as well as the new therapeutic approaches at the experimental and clinical investigation stage.]

Clinical Oncology

[Advancing therapies in metastatic castration-resistant prostate cancer]

GIULIA Baciarello, MARCO Gicci, KARIM Fizazi

[Introduction: Prostate cancer is the second most common cause of cancer world wide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the corner stone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatment shaved ramatically improved overall survival of men with mCRPC. Current therapies are basedon AR-axis inhibitors and taxane-based chemotherapies, aswell as radiopharmaceuticals and Sipuleucel T. Areas covered: The authors provide a review of the current fi eld of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies. Expert opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, aswell as in non-metastatic castrationresistant patients, it is expected that a growing subgroup of patients will be expose dearlierto chemotherapy and to AR targeted agents. It becomes then fundamental to fi nd novel strategies to over come drug resistance and further improve survival.]

Lege Artis Medicinae


FÜLÖP Vilmos

[Recurrent miscarriage and failure of in vitro fertilization and embryo transfer affect millions of women annually. It is one of the great problems of the medical community that in as many as 75% of these failures their cause is never established. Considering that recurrent abortions may have several causes including anatomical, morphological, genetic, medical, bacteriological as well as immunological abnormalities it is inevitable to pursue these kinds of examinations and tests. One part of the immunological background can be explained by autoimmune diseases while the other part of it is associated with immunopathological factors. Currently available practical testing batteries that can directly assess immunological background, as well as their importance are covered. Recently developed and mainly immunology based treatments are also described. The results generally show that immunoglobulin products can be used safely in pregnancy. In the author's institute the efficacy of this therapy has been 93.5% in cases of immune-mediated abortion. As an alternative to intravenous immunoglobulin (IVIG) therapies, partner specific platelet suspension can be used only in selected cases with proven immunological background. Therapy monitoring, that is, assessment of the functional efficacy of IVIG is possible by determining FcR blocking antibodies in the maternal serum. Based upon the functional percentage of serum blocking activity the dosage and number of treatments can be changed.]

Lege Artis Medicinae

[Gene modified T cells against cancer]


[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.]

Clinical Oncology

[Complex medical treatment of non small cell lung cancer - new challenges, new possibilities]


[Previously, it was suffi cient to differentiate small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC) in the decision making process for the therapeutic strategy of lung cancer. Recently, the situation has changed signifi cantly. There are only few new cytotoxic agents, and platinum based chemotherapy remains the standard combination in the treatment of NSCLC. In the last decade no further development has been discovered in the treatment of SCLC. However, the new molecular diagnostic and therapeutic possibilities have altered dramatically the management of NSCLC. NSCLC could not be considered as a separate entity anymore. The complex medical treatment of advanced NSCLC includes the molecular target driven therapies the histopathological subtype based chemotherapies and the immunotherapy. Immunotherapy is a new challenge in the treatment of lung cancer. Tumor-vaccines, inhibition of immune checkpoint pathways are investigated in clinical trials. Ongoing studies will defi ne the true effi cacy of these drugs. The complex combination of genes, proteins, different molecular pathways and patients characteristics, called “panomics”, are all parts of the treatment of lung cancer in the daily clinical practice.]