New analysis method for predicting the risks and effects of immunotherapy

(Uppsala University) In a new study, researchers at Uppsala University have been able to show differences in how Rituximab, a monoclonal antibody drug, interacts with the blood of healthy individuals compared to patients with chronic lymphocytic leukaemia. This has awakened hopes that this analysis method could pave the way for important breakthroughs in immunotherapy research and treatment.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news

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ankovic The p53 pathway is a desirable therapeutic target, owing to its critical role in the maintenance of genome integrity. This is exemplified in chronic lymphocytic leukemia (CLL), one of the most common adult hematologic malignancies, in which functional loss of p53 arising from genomic aberrations are frequently associated with clonal evolution, disease progression, and therapeutic resistance, even in the contemporary era of CLL targeted therapy and immunotherapy. Targeting the ‘undruggable’ p53 pathway therefore arguably represents the holy grail of cancer research. In recent years, several strategie...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
alapai Mannucci Sgambato Efremov Laurenti Membrane-bound CD200 is overexpressed in chronic lymphocytic leukemia (CLL), and there is some evidence that its soluble ectodomain (sCD200) could also be involved in the pathophysiology and the disease. However, very little is known about sCD200’s prognostic significance. sCD200 was tested at diagnosis in 272 patients with CLL and in 78 age- and sex-matched healthy subjects using a specific human CD200 (OX-2 membrane glycoprotein) ELISA kit. A significantly higher concentration of sCD200 was found in CLL patients compared to controls. In our cohort, sCD200 wa...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Chimeric antigen receptor (CAR) T cells have induced remarkable antitumor responses in B cell malignancies. Some patients do not respond because of T cell deficiencies that hamper the expansion, persistence, and effector function of these cells. We used longitudinal immune profiling to identify phenotypic and pharmacodynamic changes in CD19-directed CAR T cells in patients with chronic lymphocytic leukemia (CLL). CAR expression maintenance was also investigated because this can affect response durability. CAR T cell failure was accompanied by preexisting T cell–intrinsic defects or dysfunction acquired after infusion...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
AbstractPurpose of ReviewThe treatment options for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have expanded significantly in the last few years, including the use of new classes of oral small molecular inhibitors targeting the B cell receptor signaling pathway or the apoptosis machinery. Targeted therapy with or without immunotherapy has quickly emerged as a new standard for frontline treatment of CLL/SLL, though the previous standard chemoimmunotherapy (CIT) remains a treatment option. In this review, we present data from key clinical trials to evaluate the benefits and risks associated with differe...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research
In conclusion, therapeutic decisions must be personalized to each patient with CLL and each at risk patient must be quarantined during the SARS-CoV-2 pandemic to reduce their risk of contraction.PMID:34295383 | PMC:PMC8273855 | DOI:10.3892/ol.2021.12897
Source: Oncology Letters - Category: Cancer & Oncology Authors: Source Type: research
Clin Cancer Res. 2021 Jul 20:clincanres.0701.2021. doi: 10.1158/1078-0432.CCR-21-0701. Online ahead of print.ABSTRACTPURPOSE: In chronic lymphocytic leukemia (CLL), TP53 mutations are associated with reduced survival and resistance to standard chemo-immunotherapy (CIT). Nevertheless, the clinical impact of subclonal TP53 mutations below 10-15% variant allele frequency (VAF) remains unclear.EXPERIMENTAL DESIGN: Using a training/validation approach, we retrospectively analyzed the clinical and biological features of TP53 mutations above (high-VAF) or below (low-VAF) the previously reported 10.0% VAF threshold, as determined ...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Source Type: research
In this study, we developed an immunopeptidome-guided workflow for the design of tumor-associated off-the-shelf peptide warehouses for broadly applicable personalized therapeutics. Comparative mass spectrometry-based immunopeptidome analyses of primary chronic lymphocytic leukemia (CLL) samples, as representative example of low-mutational burden tumor entities, and a dataset of benign tissue samples enabled the identification of high-frequent non-mutated CLL-associated antigens. These antigens were further shown to be recognized by pre-existing and de novo induced T cells in CLL patients and healthy volunteers, and were ev...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
triou In the past few years, independent studies have highlighted the relevance of the tumor microenvironment (TME) in cancer, revealing a great variety of TME-related predictive markers, as well as identifying novel therapeutic targets in the TME. Cancer immunotherapy targets different components of the immune system and the TME at large in order to reinforce effector mechanisms or relieve inhibitory and suppressive signaling. Currently, it constitutes a clinically validated treatment for many cancers, including chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes with great dependency o...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
CONCLUSIONS: The CLL-CI is a simplified, CLL-specific comorbidity index which can be easily applied in clinical practice and correlates with survival in CLL.PMID:34168050 | DOI:10.1158/1078-0432.CCR-20-3993
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Source Type: research
This article will focus on the treatment approach of CLL patients with BCl2 antag onists. Treatment strategy (combined versus monotherapy; continuous versus limited duration therapy), toxicity profile, and future directions will be exposed in this review.
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
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