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International Journal of Molecular... Oct 2021Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new... (Review)
Review
Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new therapies that have contributed to the advances in treatment of certain malignancies. Immunotherapy, which has repeatedly proven to be a breakthrough therapy in melanoma, as well as B-ALL therapy with CAR T cells, are of great merit in this progress. These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Work on improving the therapy with oncolytic viruses is also progressing, and efforts are being made to improve the immunogenicity and stability of cancer vaccines. Combining various biological therapies, immunotherapy with oncolytic viruses or cancer vaccines is gaining importance in cancer therapy. New therapeutic targets are intensively sought among neoantigens, which are not immunocompromised, or antigens associated with tumor stroma cells. An example is fibroblast activation protein α (FAPα), the overexpression of which is observed in the case of tumor progression. Universal therapeutic targets are also sought, such as the neurotrophic receptor tyrosine kinase (NTRK) gene fusion, a key genetic driver present in many types of cancer. This review also raises the problem of the tumor microenvironment. Stromal cells can protect tumor cells from chemotherapy and contribute to relapse and progression. This publication also addresses the problem of cancer stem cells resistance to treatment and presents attempts to avoid this phenomenon. This review focuses on the most important strategies used to improve the selectivity of biological therapies.
Topics: Animals; Antibodies; Biological Therapy; Cancer Vaccines; Humans; Molecular Targeted Therapy; Neoplasms; Recombinant Proteins; T-Lymphocytes
PubMed: 34769123
DOI: 10.3390/ijms222111694 -
International Journal of Biological... 2021Cellular communication can be mediated by the exchange of biological information, mainly in the form of proteins and RNAs. This can occur when extracellular vesicles,... (Review)
Review
Cellular communication can be mediated by the exchange of biological information, mainly in the form of proteins and RNAs. This can occur when extracellular vesicles, such as exosomes, secreted by a donor cell are internalized by an acceptor cell. Exosomes bear specific repertoires of proteins and RNAs, indicating the existence of mechanisms that control the sorting of molecules into them. Knowledge about loadings and processes and mechanisms of cargo sorting of exosomes is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. In this review, we will discuss the molecular mechanisms associated with exosome secretion and their specific cargo sorting, with special attention to the sorting of RNAs and proteins, and thus the outcome and the emerging therapeutic opportunities of the communication between the exosome-producer and recipient cells.
Topics: Biological Therapy; Biomarkers; Exosomes; Humans; Organelle Biogenesis; Secretory Pathway
PubMed: 33390841
DOI: 10.7150/ijbs.53671 -
Rheumatology (Oxford, England) Dec 2021In this review, the results of recent and ongoing clinical trials in patients with SLE are discussed. After many unsuccessful trials in the past decade, belimumab was... (Review)
Review
In this review, the results of recent and ongoing clinical trials in patients with SLE are discussed. After many unsuccessful trials in the past decade, belimumab was the first biologic specifically designed for SLE that met its primary end point. At the same time, studies on the pathophysiology of SLE have further elucidated the pathways involved in the disease, which has led to the identification of new possible therapeutics and has encouraged the initiation of new trials. These new drugs include biologics that target B cells, T cells and type 1 interferons, and small molecules that inhibit kinases. Other therapeutics aim to restore immunological balance by restoring tolerance. Results from phase II and even phase III trials are promising and it is likely that some of the therapeutics discussed will receive approval in the following years. Hopefully, this will allow for more tailor-made medicine for SLE patients in the future.
Topics: Biological Therapy; Humans; Lupus Erythematosus, Systemic
PubMed: 34951924
DOI: 10.1093/rheumatology/keab498 -
Rheumatology International Aug 2023Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its variable course makes it difficult to standardize patient treatment. This article aims at a... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its variable course makes it difficult to standardize patient treatment. This article aims at a literature review on available drugs for treating SLE and on drugs that have shown therapeutic effects in this disease. The PubMed/MEDLINE electronic search engine was used to identify relevant studies. This review presents the current therapeutic options, new biological therapies, and combination therapies of biologics with standard immunosuppressive and immunomodulating drugs. We have also underlined the importance to implement the treat-to-target strategy aimed at reducing or discontinuing therapy with glucocorticosteroids (GCs). The awareness of the benefits and risks of using GCs helps in refining their dosage and thereby obtaining a better safety profile. The advent of biological targeted therapies, and more recently, low-molecular-weight compounds such as kinase inhibitors, initiated numerous clinical trials in SLE patients and led to the approval of two biological drugs, belimumab, and anifrolumab, for SLE treatment. Progress in the treatment of SLE was reflected in the 2019 and 2021 recommendations of the European Alliance of Associations for Rheumatology (EULAR). However, a mass of recent clinical research data requires continuous consolidation to optimize patient outcomes.
Topics: Humans; Lupus Erythematosus, Systemic; Immunosuppressive Agents; Biological Therapy; Glucocorticoids; Combined Modality Therapy
PubMed: 37171669
DOI: 10.1007/s00296-023-05306-5 -
Rheumatology (Oxford, England) Dec 2021SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely... (Review)
Review
SS is a chronic, autoimmune condition characterized by lymphocytic infiltration of the exocrine glands and B-cell dysfunction. Current treatment strategies are largely empirical and offer only symptomatic relief for patients. There are no proven treatments that alter disease progression or treat the systemic manifestations of disease. B-cell depletion is used in patients with systemic disease but its overall clinical efficacy has not been demonstrated in two large randomized controlled trials. Studies are now focussing on alternative strategies to target B-cells, including co-stimulation targets, with promising data. It is increasingly clear that clinical trials in SS will require patient stratification and relevant and sensitive outcome measures to identify successful treatment modalities.
Topics: B-Lymphocytes; Biological Therapy; Humans; Sjogren's Syndrome
PubMed: 34951923
DOI: 10.1093/rheumatology/keab466 -
Stem Cells Translational Medicine Nov 2021Umbilical cord blood transplantation (UCBT) has been performed in the clinic for over 30 years. The biological and immunological characteristics of umbilical cord... (Review)
Review
Umbilical cord blood transplantation (UCBT) has been performed in the clinic for over 30 years. The biological and immunological characteristics of umbilical cord blood (UCB) have been re-recognized in recent years. UCB, previously considered medical waste, is rich in hematopoietic stem cells (HSCs), which are naïve and more energetic and more easily expanded than other stem cells. UCB has been identified as a reliable source of HSCs for allogeneic hematopoietic stem cell transplantation (allo-HSCT). UCBT has several advantages over other methods, including no harm to mothers and donors, an off-the-shelf product for urgent use, less stringent HLA match, lower incidence and severity of chronic graft-vs-host disease (GVHD), and probably a stronger graft-vs-leukemia effect, especially for minimal residual disease-positive patients before transplant. Recent studies have shown that the outcome of UCBT has been improved and is comparable to other types of allo-HSCT. Currently, UCBT is widely used in malignant, nonmalignant, hematological, congenital and metabolic diseases. The number of UCB banks and transplantation procedures increased exponentially before 2013. However, the number of UCBTs increased steadily in Asia and China but decreased in the United States and Europe year-on-year from 2013 to 2019. In this review, we focus on the development of UCBT over the past 30 years, the challenges it faces and the strategies for future improvement, including increasing UCB numbers, cord blood unit selection, conditioning regimens and GVHD prophylaxis for UCBT, and management of complications of UCBT.
Topics: Cord Blood Stem Cell Transplantation; Fetal Blood; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Transplantation Conditioning
PubMed: 34724722
DOI: 10.1002/sctm.20-0495 -
Current Gastroenterology Reports Jun 2020Biologics for the treatment of inflammatory bowel disease (IBD) have been transformative to the therapeutic goals in the pediatric population. We review the biologics... (Review)
Review
PURPOSE OF REVIEW
Biologics for the treatment of inflammatory bowel disease (IBD) have been transformative to the therapeutic goals in the pediatric population. We review the biologics used to treat IBD, highlighting the importance of patient selection, dosing considerations, and therapeutic drug monitoring in children.
RECENT FINDINGS
Infliximab is well-established as a safe and efficacious therapy for Crohn's disease and ulcerative colitis. Both dose escalation strategies and therapeutic drug monitoring increase the likelihood of response to anti-TNFα therapies. Early real-world experience of vedolizumab and ustekinumab in pediatric IBD shows promising results, including clinical response rates comparable to what is seen in adults, but there are limited data using them as first-line therapies. Biologic therapies have improved outcomes in pediatric IBD, including achieving mucosal healing as well as improved growth and pubertal development. Therapeutic drug monitoring improves likelihood of response to anti-TNFα therapies, but further studies for vedolizumab and ustekinumab are necessary.
Topics: Antibodies, Monoclonal, Humanized; Biological Products; Biological Therapy; Child; Dose-Response Relationship, Drug; Drug Monitoring; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab; Patient Selection; Ustekinumab
PubMed: 32542562
DOI: 10.1007/s11894-020-00773-3 -
Leukemia May 2022The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated... (Review)
Review
Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and...
The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated with more recently approved immunotherapeutic agents and molecular targeted drugs for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Novel antibody based treatment approaches (inotuzumab ozogamicin, gemtuzumab ozogamicin, flotetuzumab), isocitrate dehydrogenases inhibitors (ivosidenib, enasidenib, olutasidenib), FLT3 kinase inhibitors (gilteritinib, midostaurin, quizartinib), a hedgehog inhibitor (glasdegib) as well as a BCL2 inhibitor (venetoclax) were reviewed with respect to their mode of action, their immunosuppressive potential, their current approval and the infectious complications and febrile neutropenia reported from clinical studies. Evidence-based recommendations for prevention and management of infectious complications and specific alerts regarding the potential for drug-drug interactions were developed and discussed in a plenary session with the panel of experts until consensus was reached. The set of recommendations was posted on the ECIL website for a month for comments from members of EBMT, EORTC, ICHS and ELN before final approval by the panelists. While a majority of these agents are not associated with a significantly increased risk when used as monotherapy, caution is required with combination therapy such as venetoclax plus hypomethylating agents, gemtuzumab ozogamicin plus cytotoxic drugs or midostaurin added to conventional AML chemotherapy.
Topics: Antibodies, Monoclonal; Biological Therapy; Febrile Neutropenia; Humans; Immunocompromised Host; Infections; Leukemia, Myeloid, Acute; Practice Guidelines as Topic; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35368047
DOI: 10.1038/s41375-022-01556-7 -
Stem Cell Reviews and Reports Jun 2022Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine,... (Review)
Review
Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broad perspective in cell-based therapies. Therefore, it is not surprising that MSCs have been the broadly used adult stem cells in clinical trials. To gain better insights into the current applications of MSCs in clinical applications, we perform a comprehensive review of reported data of MSCs clinical trials conducted globally. We summarize the biological effects and mechanisms of action of MSCs, elucidating recent clinical trials phases and findings, highlighting therapeutic effects of MSCs in several representative diseases, including neurological, musculoskeletal diseases and most recent Coronavirus infectious disease. Finally, we also highlight the challenges faced by many clinical trials and propose potential solutions to streamline the use of MSCs in routine clinical applications and regenerative medicine.
Topics: Adult; Adult Stem Cells; Cell- and Tissue-Based Therapy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 35344199
DOI: 10.1007/s12015-022-10369-1 -
Clinical Microbiology Reviews Jun 2020The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as... (Review)
Review
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
Topics: Biological Products; Humans; Immunomodulation; Immunosuppression Therapy; Opportunistic Infections; Risk Factors
PubMed: 32522746
DOI: 10.1128/CMR.00035-19