Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 7, 2020

The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, analysis cancer patients within pre- post-therapeutic period is required to identify several types cells, which carry a risk for disease progression subsequent relapse. Cancer stem cells (CSCs) are subpopulation tumor that can drive initiation cause relapses. At time point initiation, CSCs originate from either differentiated or adult tissue resident cells. Due their importance, characterize have been identified correlated prognosis. However, shown display high plasticity, changes phenotypic functional appearance. Such induced by chemo- radiotherapeutics as well senescent alterations microenvironment. Induction senescence causes shrinkage modulating an anti-tumorigenic environment undergo growth arrest immune attracted. Besides these positive effects after therapy, also negative displayed post-therapeutically. These unfavorable directly promote stemness CSC plasticity phenotypes, activating pathways non-CSCs, promoting escape activation pathways. end, all lead relapse metastasis. This review provides overview most frequently used markers implementation focussing on deadliest solid (lung, stomach, liver, breast colorectal cancers) hematological (acute myeloid leukemia, chronic leukemia) cancers. Furthermore, it gives examples how might be influenced therapeutics, such radiotherapy, It points out, crucial monitor residual CSCs, pro-tumorigenic senescence-associated secretory phenotype follow-up using specific biomarkers. As future perspective, targeted immune-mediated strategy chimeric antigen receptor based approaches removal remaining chemotherapy-resistant personalized therapeutic approach discussed.

Language: Английский

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Interleukins in cancer: from biology to therapy

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(8), P. 481 - 499

Published: June 3, 2021

Language: Английский

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Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: May 3, 2021

Abstract Harnessing the power of immune cells, especially T to enhance anti-tumor activities has become a promising strategy in clinical management hematologic malignancies. The emerging bispecific antibodies (BsAbs), which recruit cells tumor exemplified by cell engagers (BiTEs), have facilitated development immunotherapy. Here we discussed advances and challenges BiTE therapy developed for treatment Blinatumomab, first approved acute lymphocytic leukemia (ALL), is appreciated its high efficacy safety. Recent studies focused on improving BiTEs optimizing regimens refining molecular structures BiTEs. A considerable number cell-recruiting are potentially effective malignancies been derived from elucidation mechanisms action neonatal techniques used construction BsAbs can improve hematological This review summarized features with special focus preclinical experiments studies.

Language: Английский

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Emerging agents and regimens for AML

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: March 23, 2021

Abstract Until recently, acute myeloid leukemia (AML) patients used to have limited treatment options, depending solely on cytarabine + anthracycline (7 3) intensive chemotherapy and hypomethylating agents. Allogeneic stem cell transplantation (Allo-SCT) played an important role improve the survival of eligible AML in past several decades. The exploration genomic molecular landscape AML, identification mutations associated with pathogenesis understanding mechanisms resistance from excellent translational research helped expand options quickly few years, resulting noteworthy breakthroughs FDA approvals new therapeutic treatments patients. Targeted therapies combinations different classes agents overcome further expanded improved survival. Immunotherapy, including antibody-based treatment, inhibition immune negative regulators, possible CAR T cells might armamentarium for AML. This review is intended summarize recent developments

Language: Английский

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Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer

Cancer Discovery, Journal Year: 2020, Volume and Issue: 11(1), P. 45 - 58

Published: Dec. 4, 2020

Abstract Chimeric antigen receptor (CAR) engineering of T cells has revolutionized the field cellular therapy for treatment cancer. Despite this success, autologous CAR-T have recognized limitations that led to investigation other immune effector as candidates CAR modification. Recently, natural killer (NK) emerged safe and effective platforms engineering. In article, we review advantages, challenges, preclinical clinical research advances in NK cell cancer immunotherapy. We also briefly consider feasibility potential benefits applying vehicles expression. Significance: can redirect specificity cells, converting them a much more potent weapon combat cells. Expanding strategy effectors beyond conventional lymphocytes could overcome some paving way safer off-the-shelf products.

Language: Английский

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Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Dec. 18, 2020

Abstract Acute myeloid leukemia (AML) is the most common form of acute in adults and second children. Despite this, very little improvement survival rates has been achieved over past few decades. This partially due to heterogeneity AML need for more targeted therapeutics than traditional cytotoxic chemotherapies that have a mainstay therapy 50 years. In 20 years, research diversifying approach treating by investigating molecular pathways uniquely relevant cell proliferation survival. Here we review development novel targeting apoptosis, receptor tyrosine kinase (RTK) signaling, hedgehog (HH) pathway, mitochondrial function, DNA repair, c-Myc signaling. There an impressive effort into better understanding diversity characteristics here highlight important preclinical studies supported therapeutic continue promote new ways target cells. addition, describe clinical investigations led FDA approval therapies ongoing trials pathways. We also complexity stem cells (LSCs) as addressing relapse remission targetable are unique LSC comprehensive details what currently understand about signaling support exceptional which disrupt them.

Language: Английский

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From CAR-T Cells to CAR-NK Cells: A Developing Immunotherapy Method for Hematological Malignancies

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Aug. 6, 2021

The approval of CD19 chimeric antigen receptor (CAR)-engineered T (CAR-T) cell products in B-cell malignancies represents a breakthrough CAR-T immunotherapy. However, the remaining limitations concerning graft-versus-host disease (GVHD) and other adverse effects (e.g., cytokine release syndromes [CRS] neurotoxicity) still restrict their wider applications. Natural killer (NK) cells have been identified as promising candidates for CAR-based cellular immunotherapy because unique characteristics. No HLA-matching restriction abundant sources make CAR-engineered NK (CAR-NK) potentially available to be off-the-shelf that could readily immediate clinical use. Therefore, researchers gradually shifted focus from CAR-NK hematological malignancies. This review discusses current status applications malignancies, well advantages compared with cells. It also challenges prospects regarding

Language: Английский

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Chimeric antigen receptor (CAR) natural killer (NK)‐cell therapy: leveraging the power of innate immunity

British Journal of Haematology, Journal Year: 2020, Volume and Issue: 193(2), P. 216 - 230

Published: Nov. 20, 2020

Summary Chimeric antigen receptor (CAR) T cells are a rapidly emerging form of cancer treatment, and have resulted in remarkable responses refractory lymphoid malignancies. However, their widespread clinical use is limited by toxicity related to cytokine release syndrome neurotoxicity, the logistic complexity manufacturing, cost time‐to‐treatment for autologous CAR‐T cells, risk graft‐ versus ‐host disease (GvHD) associated with allogeneic cells. Natural killer (NK) emerged as promising source CAR‐based therapies due ready availability safety profile. NK part innate immune system, providing first line defence against pathogens They produce cytokines mediate cytotoxicity without need prior sensitisation ability interact with, activate other immunotherapy can be generated from multiple sources, such expanded or peripheral blood, umbilical cord haematopoietic stem induced pluripotent well cell lines. Genetic engineering express CAR has shown impressive preclinical results currently being explored trials. In present review, we discuss both trial progress made field NK‐cell therapy, strategies overcome challenges encountered.

Language: Английский

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Biological Characteristics of Umbilical Cord Mesenchymal Stem Cells and Its Therapeutic Potential for Hematological Disorders

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: May 3, 2021

Umbilical cord mesenchymal stem cells (UC-MSCs) are a class of multifunctional isolated and cultured from umbilical cord. They possessed the characteristics highly self-renewal, multi-directional differentiation potential low immunogenicity. Its application in field tissue engineering gene therapy has achieved series results. Recent studies have confirmed their inhibiting tumor cell proliferation migration to nest cancer. The ability UC-MSCs support hematopoietic microenvironment suppress immune system suggests that they can improve engraftment after transplantation, which shows great treatment hematologic diseases. This review will focus on latest advances biological mechanism hematological

Language: Английский

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The EBMT/EHA CAR-T Cell Handbook

Springer eBooks, Journal Year: 2022, Volume and Issue: unknown

Published: Jan. 1, 2022

Language: Английский

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