Clinical Oncology

[Tumor vaccination]

LACZÓ Ibolya, PIKÓ Béla

MAY 10, 2018

Clinical Oncology - 2018;5(02)

[Although cancer immunotherapy was initiated by William Coley more than a century ago, the fi eld of cancer vaccines is in an early stage of development. Only recently, major advances in cellular and molecular immunology have allowed a comprehensive understanding of the interaction between the immune system and the tumor. Data from several preclinical and clinical trials have confi rmed the positive effect of the cancer vaccines which accompanied in several cases by positive clinical outcomes. In our article we try to discuss the new cancer vaccine strategies which are under development or in a clinical phase stage.]



Further articles in this publication

Clinical Oncology

[Recent strategies in the chemoterapy of soft tissue tumors]

PÁPAI Zsuzsanna, KISS Nóra

[Conventional adjuvant therapy is, in most cases, either the well-known standard doxorubicin monotherapy or the combination of doxorubicin + ifosfamide. No clear guideline has been developed yet - adjuvant therapy is recommended in cases with high grade, larger than 10 cm, sarcoma, where surgery hasn’t been suffi ciently radical, and adjuvant radiotherapy may not be advisable. In locally advanced tumors, due to the requirements of limb salvage, isolated limb perfusion is recommended. As a new compound, hafnium-oxide nanoparticles (NBTXR3) can be useful in local therapy: combining intratumoral injection and radiotherapy may be a fl agship initiative, however further investigations are necessary. In the treatment of metastatic tumors, beside the standard methods, new, targeted treatments are becoming more and more prevalent: in leiomyosarcomas trabectedine, pazopanib and olaratumab; in liposarcomas trabectedine and eribulin; in synovial sarcomas pazopanib; and in imatinib-resistant GIST, sunitinib and regorafenib. Soft tissue sarcomas are rare tumors categorized as heterogeneous histological subtypes. In their treatment, it is key to customize the treatment based on these subtypes and interdisciplinary collaboration with the orthopedic surgeon, the pathologist and the radiotherapist to determine the suitable therapy for each individual.]

Clinical Oncology

[Fusions in solid tumors]


[Genetic fusions are the cosequence of genomic rearrangement including chromosomal inversion, interstitial deletion, duplication, amplifi cation, translocation. Fusions can influence tumor development and progression. Fusions fi rst discovered in hematological malignances (e.g. BCR-ABL), butlater more and more were identified dueto the higly sensitive NGS. It has been found that the oncogenic fusions are in minority in a given tumor. Today, some fusions were apprevedas targets (ALK, ROS1, PDGFB) by FDA. Asino ther targeted therapy resistance is in evitable, which is a very important challenge for newly designed drugs.]

Clinical Oncology

[Fluid in preformed cavity to malignancy]


[The malignancy associated fl uids like pleural effusion, ascites and pericardiac fl uid are a common problems in patients with cancer. Despite the existence of typical types of cancer for these fl uid accumulations, nearly all types of cancer can cause malignancy associated fl uids. The presentation of these fl uids is generally a sign for disease progression, and forecast a poor prognosis. The prognostic factors include the type of cancer, the response to antitumorous therapy and the general condition of the patient, which include age, ECOG status and so on. In most of the cases, the treatment of these fl uid accumulations is supposed to decrease the symptoms, and guarantee an acceptable quality of life, consequently the treatment has a palliative intent. Indeed, there are some exceptions such as cardiac tamponade. From the large scale of available treatments, we have to choose upon careful risk analysis.]

Clinical Oncology

[News from the World]

Clinical Oncology

[Cardiotoxicity caused by fluoropirimides]

PIA Österlund

[One of the most effective traditional anticancer drugs are the fluoropyrimidines. The most challenging problem of the treatment is the cardiotoxicity. This review focuses on cardiotoxicity based on the references as well as personal experiences. The severness of the cardiotoxicity has a rang euptofatal outcome. There for eit is mandatory to monitor heart condition during the treatment with fluoropyrimidines.]

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Clinical Oncology

[Combination of radiotherapy and immunotherapy]

HIDEGHÉTY Katalin, BRUNNER Szilvia, SZABÓ Zoltán Imre, SZABÓ Emília Rita, POLANEK Róbert, TŐKÉS Tünde

[Increasing experimental and clinical evidences demonstrated the synergic effect between the rapidly implemented immunotherapy and advanced forms of focal radiotherapy, not only on the elimination of the irradiated lesion, but also on the enhancement the immune-mediated systemic anti-tumoral activity. It is essential for gaining the most benefi t from the combination of the two modalities to select the appropriate patients, to defi ne the irradiation parameters, such as radiation quality (ie. particle) dosage, (total dose, fraction number) size of the target volume, the use of other supportive and anti-tumor drugs. In this review, we provide an update for the daily oncological practice on the data accumulated up to now on the molecular basis and patomechanism of enhancing radio-immune effect and clinical results, and highlight the most important parameters, which may increase the abscopal effect of ionizing radiation, thereby increasing the effectiveness of immunotherapy. However, development of clinical guidelines for benefi cial integration of immunotherapy and radiotherapy could be expected after evaluation the result of currently ongoing numerous (> 100) clinical trials. If the preclinical results will be confi rmed clinically, it could lead to paradigm shift in the use of ionizing radiation.]

Clinical Oncology

[Management of prostate cancer today]

PETRÁNYI Ágota Eszter, BODROGI István

[Although metastatic prostate cancer remains an incurable disease, the past years witnessed an extraordinary progress in the management of patients with castration resistant prostate cancer (CRPC). Development of novel agents that modulate the androgen receptor pathway, growth factor signaling pathways, immune functions and bone targeting machinery has been the focus of therapeutic strategies because of its signifi cance in the biology of prostate cancer progression. The arrival of several new agents — cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, denosumab and radium-223 — is changing the options and management of patients with metastatic castration resistant prostate cancer (mCRPC). Prostate cancer is a heterogeneous disease, therefore, in treatment must be considered the clinical characteristics of the disease as it manifests in an individual patient. The aim of this review is to summarize the most important new fi ndings for metastatic prostate cancers according to the different molecular pathways and to discuss their potential role on the management of this disease.]

Clinical Neuroscience

[Fingolimod therapy in multiple sclerosis - the issue of the pathomechanism]

TAR Lilla, VÉCSEI László

[Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system with neurodegenerative chararacteristics. The newly discovered per os administrable drug fingolimod (FTY720) has a different mechanism of action than the current disease-modifying therapies. In vivo the drug binds to four out of the five sphingosine-1-phosphate receptors after phosphorylation. Fingolimod-phosphate (FTY720-P) causes internalization and degradation of the sphingosine-1-phosphate receptors in the membrane of lymphocytes thus in contrast to sphingosine-1-phosphate it acts like a functional antagonist. In experimental autoimmune encephalomyelitis - an animal model of multiple sclerosis - fingolimod blocks the sphingosine-1-phosphate gradient controlled lymphocyte egress from the lymph nodes and therefore reduces the peripheral lymphocyte count especially the encephalitogenic Th17 subset is reduced. Modulation of the sinus lining and blood-brainbarrier constructing endothelial cells also contributes to the complex mechanism of action. Additionally due to its liphohilic nature fingolimod is able to penetrate the blood brain barrier thus, beside its peripheral effects the drug can probably modulate the cells of the central nervous system directly. Presumably it can reduce neurodegeneration caused by astrogliosis through modification of astrocyte and oligodendrocyte activity. The results of current clinical studies are holding out with bright prospective in the aspect of either the favourable effects or the well tolerated side effects.]

Lege Artis Medicinae

[Intravenous immunoglobulin immunotherapy in immune mediated habitual abortions]


[INTRODUCTION - Based upon international and domestic research data authors summerize the humoral and cellular im­munregulatory disorders which can be found in the background of “immune me­diated abortions” (IMA). PATIENTS AND METHODS - Within the frame of a home research program a special examination protocol was elaborated in order to sepatare alloimmune habitual abortions from autoimmune and non immune backgrounds. After all other causes were excluded erythrocyte antibody inhibition assay (EAI) was used for measuring the serum level of FcgRII receptor blocking IgG antibody, because its lack an important diagnostic parameter. Among the cell mediated immunofuntional tests the mixed lymphocyte culture reaction (MLC) was the most useful. During the roughly last 16 years 67 out of 76 selected alloimmun IMA patients were administered Intratect IVIG treatment without any particular selection among them. IVIG treatment was first applied on the completed 5-6th week of pregnancy and doses of 0,3-0,4g/kg bodyweight per oc­casion were given 3 times with 3-week intervals. RESULTS - Altogether a significant rise in the serum level of blocking antibodies was shown after each IVIG treatment although a slight decrease was seen after every given dose. Of the 67 IMA patients 54 carried infants to term during the study period. In 4 cases of abortion no cause was identified with post hoc diagnosis. Thus the success rate of this type of IVIG therapy was 93.1% (58/54). Conclusion - In approprietly selected alloimmun IMA cases the IVIG generated immunoregulatory and antiimflammatory pathways may contribute to its net positive reproductive effect.]

Clinical Oncology

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


[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.]