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Background/aim: To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials., Patients and Methods: Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group., Results: Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy., Conclusion: Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Chimeric antigen receptor T (CAR-T) cells are specifically modified T cells which bear recombinant receptors, present at the cell surface and devoted to detect selected antigens of cancer cells, and due to the presence of transmembrane and activation domains, able to eliminate the latter ones. The use of CAR-T cells in anti-cancer therapies is a relatively novel approach, providing a powerful tool in the fight against cancer and bringing new hope for patients. However, despite huge possibilities and promising results of preclinical studies and clinical efficacy, there are various drawbacks to this therapy, including toxicity, possible relapses, restrictions to specific kinds of cancers, and others. Studies desiring to overcome these problems include various modern and advanced methods. One of them is transcriptomics, a set of techniques that analyze the abundance of all RNA transcripts present in the cell at certain moment and under certain conditions. The use of this method gives a global picture of the efficiency of expression of all genes, thus revealing the physiological state and regulatory processes occurring in the investigated cells. In this review, we summarize and discuss the use of transcriptomics in studies on and applications of CAR-T cells, especially in approaches focused on improved efficacy, reduced toxicity, new target cancers (like solid tumors), monitoring the treatment efficacy, developing novel analytical methods, and others. [ABSTRACT FROM AUTHOR]

Simple Summary: The complement system can be exploited by anticancer antibody-based therapeutics. Activation of the classical complement pathway by the heavy chain of antibodies eventually leads to the lysis of target cells. However, overexpression of complement inhibitors by tumor cells limits the therapeutic efficacy. We designed and produced recombinant gain-of-function variants of complement C2 protein that counteract the activity of complement inhibitors. The dominant character of designed mutations in C2 allows supplementation of human serum with recombinant proteins for enhancing the cytocidal activity of complement-activating antibodies. In vitro functional assays demonstrate that this strategy is compatible with several clinically approved antibodies. The molecular target for the classical complement pathway (CP) is defined by surface-bound immunoglobulins. Therefore, numerous anticancer monoclonal antibodies (mAbs) exploit the CP as their effector mechanism. Conversely, the alternative complement pathway (AP) is spontaneously induced on the host and microbial surfaces, but complement inhibitors on host cells prevent its downstream processing. Gain-of-function (GoF) mutations in the AP components that oppose physiological regulation directly predispose carriers to autoimmune/inflammatory diseases. Based on the homology between AP and CP components, we modified the CP component C2 so that it emulates the known pathogenic mutations in the AP component, factor B. By using tumor cell lines and patient-derived leukemic cells along with a set of clinically approved immunotherapeutics, we showed that the supplementation of serum with recombinant GoF C2 variants not only enhances the cytocidal effect of type I anti-CD20 mAbs rituximab and ofatumumab, but also lowers the threshold of mAbs necessary for the efficient lysis of tumor cells and efficiently exploits the leftovers of the drug accumulated in patients' sera after the previous infusion. Moreover, we demonstrate that GoF C2 acts in concert with other therapeutic mAbs, such as type II anti-CD20, anti-CD22, and anti-CD38 specimens, for overcoming cancer cells resistance to complement attack. [ABSTRACT FROM AUTHOR]