Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Sunday, December 19, 2021

Chimeric antigen receptor T cells

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Bull Cancer. 2021 Oct;108(10S):S55-S64. doi: 10.1016/j.bulcan.2021.08.003.

ABSTRACT

Chimeric antigen receptor T-cell (CAR T-cells) therapies which are genetically modified T lymphocyte targeting tumor antigens have modified therapeutic landscape in hematology. Aggressive B cells lymphoma are currently treated in daily practice with anti-CD19 CAR T. In indolent B cell lymphomas, their efficacy has been established by recent clinical trials. Longer follow-up evaluation is needed to determine their added value in a field where approved strategies already provide high long-term survival rates. They will also be challenged by another immunotherapy with bispecific antibodies. In chronic lymphoid leukemia, early phase trials have identified several limitations related to the immune context of this disease, but associations with targeted therapy like ibrutinib are very promising. In this moving therapeutic landscape, molecular and cellular eng ineering progress will increase the capacities of these new cellular-based therapies.

PMID:34920808 | DOI:10.1016/j.bulcan.2021.08.003

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CARTi: The French-speaking group for the harmonization of immune monitoring in patients treated with CAR-T cells

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Bull Cancer. 2021 Oct;108(10S):S141-S142. doi: 10.1016/j.bulcan.2021.06.006.

NO ABSTRACT

PMID:34920796 | DOI:10.1016/j.bulcan.2021.06.006

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Bispecific antibodies: An old story with a bright future… with CAR-T cells!

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Bull Cancer. 2021 Oct;108(10S):S168-S180. doi: 10.1016/j.bulcan.2021.02.016.

ABSTRACT

CAR-T cells originate from two different approaches, cellular immunotherapy based on tumor immunosurveillance by T lymphocytes, combined with molecular engineering of bispecific antibodies and antibody fragments. The latter makes it possible to retarget immune effector cytotoxic cells (such as NK cells and T lymphocytes) to tumor cells through the binding to tumor-associated antigens. We present herein the history of bispecific antibodies, highlighting how such antibodies played a major role in CAR-T cell development. We will first evoke how antibody engineering led to the construction of various bispecific formats, in particular using the single chain Fv fragment (scFv) which has been used as the initial building block to generate chimeric bi-, tri- or multifunctional molecules. We will also describe how bispecific antibodies, either full IgG or as s cFv or F(ab')2 format, directed against Fcγ receptors or CD3ɛ and against tumor-associated antigens, induce a potent anti-tumor cytotoxicity following the recruitment and activation of immune effector cells, including CD3+ T lymphocytes. These anti-tumor effects have been translated into the clinics, especially to treat malignant hemopathies. At last, recently generated bispecific CAR-T cells suggest that the embrace between cell therapy and bispecific antibodies is not over and that we are yet to witness further discoveries enabling these cells to be even more efficient.

PMID:34920800 | DOI:10.1016/j.bulcan.2021.02.016

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CAR-T cell: Toxicities issues: Mechanisms and clinical management

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Bull Cancer. 2021 Oct;108(10S):S117-S127. doi: 10.1016/j.bulcan.2021.05.003.

ABSTRACT

CAR-T cells are modified T cells expressing a chimeric antigen receptor targeting a specific antigen. They have revolutionized the treatment of B cell malignancies (aggressive lymphomas, B-ALL), and this has raised hopes for application in many other pathologies (myeloma, AML, solid tumors, etc.). However, these therapies are associated with novel and specific toxicities (cytokine release syndrome and neurotoxicity). These complications, although mostly managed in a conventional hospitalization unit, can sometimes be life threatening, leading to admission of patients to the intensive care unit. Management relies mainly on anti-IL6R (tocilizumab) and corticosteroids. However, the optimal treatment regimen is still a matter of debate, and the management of the most severe forms is even less well codified. In addition to CRS and ICANS, infections, cytope nia and hypogammaglobulinemia are other frequent complications. This article reviews the mechanisms, risk factors, clinical presentation, and management of these toxicities.

PMID:34920794 | DOI:10.1016/j.bulcan.2021.05.003

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T cell-based immunotherapies in solid tumors

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Bull Cancer. 2021 Oct;108(10S):S96-S108. doi: 10.1016/j.bulcan.2021.06.004.

ABSTRACT

In solid tumors, adoptive T cell therapies based on ex vivo amplification of antitumor T cell are represented by three main complementary approaches : (i) tumor infiltrating lymphocytes (TILs) which are amplified in vitro before reinjection to the patient, (ii) chimeric antigen receptor (CAR) engineered T cells and (iii) T cell receptor (TCR) engineered T cells. Despite encouraging results, some obstacles remain, such as optimal target selection and tumor microenvironment. In this Review, we discuss pros and cons of these different therapeutic strategies that may open new perspectives in the treatment of solid tumors.

PMID:34920813 | DOI:10.1016/j.bulcan.2021.06.004

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CAR-T CELLS: How does the EBMT registry monitor European activities, identify hurdles and prepare for changes in regulations

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Bull Cancer. 2021 Oct;108(10S):S155-S161. doi: 10.1016/j.bulcan.2021.08.004.

ABSTRACT

CAR-T Cells are gene therapy medicinal products, a subcategory of Advanced Therapy Medicinal Products as defined in the EC Regulation 1394/2007. They may represent the first example of such medicinal products that are industry-manufactured and commercialized on a large scale. Their very nature, their manufacturing processes, pricing and conditions upon which they were approved by regulatory agencies, all lead the latter to require long-term follow-up after marketing approval with a view for a better definition of CAR-T Cells safety profile and efficacy profile in real world conditions. Collection and analysis of data over a 15-year period of time represents a technical and political challenge. So does the a priori definition of data to be collected for a wealth of forthcoming analyses that focus on the interests of a variety of stakeholders. EBMT has been collecting and analyzing data on hematopoietic cell transplants for decades. EBMT currently works with many interested parties to collect data on patients treated with CAR-T Cells.

PMID:34920798 | DOI:10.1016/j.bulcan.2021.08.004

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The Voice Problem Impact Scales (VPIS)

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Patient-reported outcome measures (PROMs) are important for systematically assessing a person's perspectives and experiences with disease to inform clinical decision-making. However, PROMs can occasionally fail to capture subtle differences amongst subgroups. In response to this problem, the aim of the current study was to examine the convergent validity of four patient-reported voice activity and participation scales to better reflect and describe the impact of a voice problem in a patient's work, home, social and overall life.
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