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


A szerkesztők

Clinical Oncology

[News from the World]

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[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

[Radiochemotherapy - questions/answers]

PIKÓ Béla, LACZÓ Ibolya

[During chemoradiotherapy the two main non-surgical anticancer methods are combined to improve the treatment outcomes. The theoretical possibilities of interactions and the most frequently used drugs will be presented here, emphasizing that although both the radiation therapy and the drugs need to be administered in full dose in practice considering the summarization of side effects we often have to make compromises. The treatments of the most frequent indications (brain, head and neck, oesophagus, lung, stomach, pancreas, rectum, bladder, cervix, soft tissue sarcoma) will be demonstrated. Since there are several drugs and drug combinations that are not included in the Hungarian registered anticancer therapies, for their off-label use the permission of the National Institute of Pharmacy and Nutrition is required. To choose the optimal treatment (during planning the optimal place of chemoradiotherapy, agents and doses) the opinion of a multidisciplinary team is necessary]

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.]

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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.]