Emerging immunological drugs for chronic lymphocytic leukemia

Robak, Paweł; Smolewski, Piotr; Robak, Tadeusz

doi:10.1517/14728214.2015.1046432

Cited by 9 publications

(5 citation statements)

References 136 publications

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“…The advent of monoclonal antibodies directed against CD20 and CD52 heralded the beginning of the targeted therapy revolution1 and these antibodies have since been joined by small molecule inhibitors, which target phosphoinositide 3-kinase (idealisib)2, the Bruton's tyrosine kinase (ibrutinib)345 and BH3 mimetics, which inhibit BCL-2 (Venetoclax and Navitoclax)678. Although highly effective, the increasing use of these therapies has revealed deficiencies in current strategies for disease monitoring, largely due to differential treatment responses across separate disease compartments.…”

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confidence: 99%

Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia

et al. 2017

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Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter's syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring.

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confidence: 99%

Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia

et al. 2017

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“…Most of tumours contains a variable fraction of cells manifesting markers of stem cells [113], recently with increasing frequency termed the tumour propagating cells. The cells manifest genome instability.…”

Section: How Tumors Arise -The Example Of Lung Cancer and Leukaemiasmentioning

confidence: 99%

Problems of Cancer Treatment. Part I. Theory of Treatment Based on Known Mechanisms of Anticancer Immunological Responses

Kawiak

Hoser

Domagała‐Kulawik

2017

Advances in Cell Biology

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Summary: Various processes, taking place both in cells and in their environment, are linked to carcinogenesis. This paper aims at recalling the complex mechanisms of oncogenesis, with particular attention paid to responses of the immune system. In development of solid tumours, leukaemias and lymphomas several common stages can be noted. A neoplastic disease cannot be understood considering only phenomena of genetic mutations. Neoplastic cells are characterised by an extensive antigenic variability and resistance to apoptosis. The cells create around them a microenvironment which protects them from defensive activity of the host. In the paper we present the recognised mechanisms of anti-neoplastic defense as well as several elements allowing the solid tumours and leukaemias to escape from the immune surveillance. The generally accepted treatment of tumours aims at reducing numbers of tumour cells. Following resection of a tumour, radiotherapy or chemotherapy, the parallel or consecutive stage of treatment was found to involve an increase in number of clones of immune system cells. One of the ways in which the immune system can be activated involves autovaccination of the host with own neoplastic cells in an apoptosis. However, attempts of such a therapy frequently brought no expected results due to blocked activity of cytotoxic cells. Therefore, the subsequent stage in activation of the immune system should involve elimination of the tumor-mobilized blockade of the system. Attempts toward this aim include neutralization of the tumour-blocked cytotoxic properties of defensive cells, first of all T lymphocytes. The recognized mechanisms of blocking T cells activity in the PD-1/PD-L1 system or due to inhibition of activation by CTLA-4 molecule provided rationale for development of effective tumour immunotherapy approaches. Keywords

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“…These include ocaratuzumab, which is a type I, third-generation humanized Fab-and Fc-engineered IgG1 antibody with increased ability to mediate antibody- dependent cellular cytotoxicity [102,103]. Another available antibody is veltuzumab, also a type I antibody, which is structurally and functionally different from rituximab and has enhanced binding avidities and a stronger effect on CDC than rituximab.…”

Section: Inflammatory Myopathiesmentioning

confidence: 99%

“…Another available antibody is veltuzumab, also a type I antibody, which is structurally and functionally different from rituximab and has enhanced binding avidities and a stronger effect on CDC than rituximab. These drugs, among others, constitute future therapeutic options for neurological autoimmunity [102,103].…”

Section: Inflammatory Myopathiesmentioning

confidence: 99%

Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

2016

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B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurological disorders, acting as antibody-producing cells and, most importantly, as sensors, coordinators, and regulators of the immune response. B cells, among other functions, regulate the T-cell activation process through their participation in antigen presentation and production of cytokines. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules or Bcell trophic factors bestows a rational approach for treating autoimmune neurological disorders, even when T cells are the main effector cells. This review summarizes basic aspects of B-cell biology, discusses the role(s) of B cells in neurological autoimmunity, and presents anti-B-cell drugs that are either currently on the market or are expected to be available in the near future for treating neurological autoimmune disorders.

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Emerging immunological drugs for chronic lymphocytic leukemia

Abstract: The use of mAbs, BCR inhibitors and immunomodulating drugs is a promising new strategy for chemotherapy-free treatment of CLL. However, definitive data from ongoing and future clinical trials will aid in better defining the status of immunological drugs in the treatment of this disease.

Cited by 9 publications

References 136 publications

Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia

Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia

Problems of Cancer Treatment. Part I. Theory of Treatment Based on Known Mechanisms of Anticancer Immunological Responses

Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

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