scholarly journals A summary of current NKG2D-based CAR clinical trials

2021 ◽  
Author(s):  
Sophie Curio ◽  
Gustav Jonsson ◽  
Sonja Marinovic ◽  
Keyword(s):  
Clinical Trials ◽  
Tumor Cells ◽  
Treatment Options ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
New Therapeutic Approaches ◽  
Important Player ◽  
Cancer Types ◽  
Stressed Cells ◽  
Cancer Immunotherapies

Abstract Cancer immunotherapies have significantly improved patient survival and treatment options in recent years. Nonetheless, the success of immunotherapy is limited to certain cancer types and specific subgroups of patients, making the development of new therapeutic approaches a topic of ongoing research. Chimeric antigen receptor (CAR) cells are engineered immune cells that are programmed to specifically eliminate cancer cells. Ideally, a CAR recognizes antigens that are restricted to tumor cells to avoid off-target effects. NKG2D is an activating immunoreceptor and an important player in anti-tumor immunity due to its ability to recognize tumor cells and initiate an anti-tumor immune response. Ligands for NKG2D are expressed on malignant or stressed cells and typically absent from healthy tissue, making it a promising CAR candidate. Here, we provide a summary of past and ongoing NKG2D-based CAR clinical trials and comment on potential pitfalls.

scholarly journals Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 192
Author(s):  
Leonie Konczalla ◽  
Anna Wöstemeier ◽  
Marius Kemper ◽  
Karl-Frederik Karstens ◽  
Jakob Izbicki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Application ◽  
Liquid Biopsy ◽  
Cancer Diagnostics ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
New Therapeutic Approaches ◽  
Tumor Dissemination

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

scholarly journals When the endothelium scores an own goal: endothelial cells actively augment metastatic extravasation through endothelial-mesenchymal transition

2016 ◽  
Vol 310 (9) ◽  
pp. H1055-H1063 ◽  
Author(s):  
Ákos Gasparics ◽  
László Rosivall ◽  
István A. Krizbai ◽  
Attila Sebe
Keyword(s):  
Endothelial Cells ◽  
Tumor Cells ◽  
Metastatic Tumor ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
New Therapeutic Approaches ◽  
Pathological Conditions ◽  
Junctional Protein ◽  
Endothelial Mesenchymal Transition ◽  
Organ Fibrosis

Endothelial-mesenchymal transition (EndMT) is an important mechanism during organ development and in certain pathological conditions. For example, EndMT contributes to myofibroblast formation during organ fibrosis, and it has been identified as an important source of cancer-associated fibroblasts, facilitating tumor progression. Recently, EndMT was proposed to modulate endothelial function during intravasation and extravasation of metastatic tumor cells. Evidence suggests that endothelial cells are not passive actors during transendothelial migration (TEM) of cancer cells, as there are profound changes in endothelial junctional protein expression, signaling, permeability, and contractility. This review describes these alterations in endothelial characteristics during TEM of metastatic tumor cells and discusses them in the context of EndMT. EndMT could play an important role during metastatic intravasation and extravasation, a novel hypothesis that may lead to new therapeutic approaches to tackle metastatic disease.

Comorbidity of Migraine and Epilepsy in Pediatrics: A Review

2018 ◽  
Vol 33 (12) ◽  
pp. 801-808 ◽  
Author(s):  
Jasna Jancic ◽  
Vesna Djuric ◽  
Boris Hencic ◽  
John N. van den Anker ◽  
Janko Samardzic
Keyword(s):  
Genetic Basis ◽  
Treatment Options ◽  
Dietary Therapy ◽  
Channel Blockers ◽  
Therapeutic Approaches ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
New Therapeutic Approaches ◽  
Neurologic Disorders

Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders sharing many clinical features, as well as possible treatment options. This review highlights the similarities between migraine and epilepsy in pediatrics, focusing on epidemiologic, pathophysiological, genetic, clinical, and pharmacologic aspects. Despite the fact that several syndromes share symptoms of both migraine and epilepsy, further research is needed to clarify the pathophysiological and genetic basis of their comorbidity. Drugs used for prophylactic therapy of migraine and epilepsy have similar pharmacologic properties. The role of epileptic pharmacotherapy in the prophylaxis of migraine is assessed, including the use of conventional antiepileptic drugs, calcium channel blockers, and nonpharmacologic methods such as dietary therapy, supplements, and vagal nerve stimulation. Further randomized, controlled clinical trials assessing pharmacologic and nonpharmacologic methods for the treatment of both disorders are essential, in order to initiate new therapeutic approaches.

scholarly journals Clinical trials for treatment or prevention of COVID-19. A review of Clinicaltrials.gov.

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 823
Author(s):  
Martha Fors ◽  
Paloma González
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Randomized Trials ◽  
Descriptive Study ◽  
Therapeutic Approaches ◽  
Open Label ◽  
Disease Treatment ◽  
Cross Sectional ◽  
Ongoing Research ◽  
Antimalarial Agents

Background: Coronavirus disease 2019 (COVID-19) has rapidly progressed into the worst pandemic in recent years. There are currently no approved therapies to treat the disease. Several clinical trials are being conducted to evaluate therapeutic approaches. Methods: We conducted a cross-sectional descriptive study to examine the main characteristics of COVID-19-related clinical interventional trials registered with ClinicalTrials.gov  from January to March 27th, 2020. . Results: We included 519 trials, 57.6% were phase II or III, open-label and randomized trials. Disease treatment was evaluated in 75.5% of trials, while prevention was evaluated in 12.1%. A total of 243 trials were listed as recruiting, and 42.4% were not yet recruiting. Approximately 20% of the analyzed trials are investigating antimalarial agents, while 10.2% are studying the use of convalescent plasma to treat the disease. Antiretrovirals, monoclonal antibodies, the use of stem cells, nitric oxide gases and vaccines are the most commonly evaluated therapies. As of the publication of this review, none of the clinical trials had uploaded results. Conclusions: ClinicalTrials.gov is an important database that contains ongoing research trials on COVID-19This study quantifies the outcomes of COVID-19-related clinical trials.  More than 500 studies have been  analyzed finding that most of these studies are interventional clinical trials  Phase II or III evaluating drugs or biological agents for the prevention or treating COVID-19.

scholarly journals New Therapeutic Approaches for Allergy: A Review of Cell Therapy and Bio- or Nano-Material-Based Strategies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2149
Author(s):  
Juan L. Paris ◽  
Paz de la Torre ◽  
Ana I. Flores
Keyword(s):  
Cell Therapy ◽  
Treatment Options ◽  
Allergic Diseases ◽  
Immunological Tolerance ◽  
Term Treatment ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Long Term Treatment ◽  
Nano Material

Allergy constitutes a major health issue due to its large prevalence. The established therapeutic approaches (allergen avoidance, antihistamines, and corticosteroids) do not address the underlying causes of the pathology, highlighting the need for other long-term treatment options. Antigen-specific immunotherapy enables the long-term control of allergic diseases by promoting immunological tolerance to the allergen. However, efficacious immunotherapies are not available for all possible allergens, and the risk of undesired reactions during therapy remains a concern, especially in patients with severe allergic reactions. In this context, two types of therapeutic strategies appear especially promising for the future in the context of allergy: cell therapy and bio- or nano-material-based therapy. In this review, the main strategies developed this far in these two types of strategies are discussed, with several examples illustrating the different approaches.

scholarly journals Lack of consideration of sex and gender in clinical trials for COVID-19

2020 ◽  
Author(s):  
Emer Brady ◽  
Mathias Wullum Nielsen ◽  
Jens Peter Andersen ◽  
Sabine Oertelt-Prigione
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Sex And Gender ◽  
Therapeutic Approaches ◽  
Planning Stage ◽  
New Therapeutic Approaches ◽  
Analysis Phase ◽  
Potential Risks ◽  
And Gender ◽  
Sex And Gender Differences

Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences characterize the frequency and severity of pharmacological side effects. A large number of clinical trials are ongoing to develop new therapeutic approaches and vaccines for COVID-19. We investigated the inclusion of sex and/or gender in currently registered studies on ClinicalTrials.gov. Only 416 (16.7%) of the 2,484 registered SARS-CoV-2/COVID-19 trials mention sex/gender as recruitment criterion and only 103 (4.1%) allude to sex/gender in the description of the analysis phase. None of the 11 clinical trials published in scientific journals on June 2020 reported sex-disaggregated results. Hence, lack of consideration upon registration does not seem to be corrected during trial execution and reporting. Given the biological relevance and the potential risks of unwanted side effects, we urge researchers to focus on sex-disaggregated analyses already at the planning stage of COVID-19 trials.

scholarly journals Recent advances in the medical treatment of breast cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2786 ◽  
Author(s):  
Daniel A. Vorobiof
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Medical Treatment ◽  
Breast Cancer Treatment ◽  
Chemotherapeutic Drugs ◽  
Therapeutic Approaches ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Receptor Modulator ◽  
Medical Oncologists

Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs.

scholarly journals Lack of consideration of sex and gender in COVID-19 clinical studies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Emer Brady ◽  
Mathias Wullum Nielsen ◽  
Jens Peter Andersen ◽  
Sabine Oertelt-Prigione
Keyword(s):  
Clinical Trials ◽  
Scientific Journals ◽  
Sex And Gender ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Subgroup Analyses ◽  
Analytical Variable ◽  
And Gender ◽  
Sex And Gender Differences ◽  
Representative Samples

AbstractSex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences influence the frequency and severity of pharmacological side effects. A large number of clinical trials to develop new therapeutic approaches and vaccines for COVID-19 are ongoing. We investigated the inclusion of sex and/or gender in COVID-19 studies on ClinicalTrials.gov, collecting data for the period January 1, 2020 to January 26, 2021. Here, we show that of the 4,420 registered SARS-CoV-2/COVID-19 studies, 935 (21.2%) address sex/gender solely in the context of recruitment, 237 (5.4%) plan sex-matched or representative samples or emphasized sex/gender reporting, and only 178 (4%) explicitly report a plan to include sex/gender as an analytical variable. Just eight (17.8%) of the 45 COVID-19 related clinical trials published in scientific journals until December 15, 2020 report sex-disaggregated results or subgroup analyses.

scholarly journals Clinical Trials Based on Mesenchymal Stromal Cells are Exponentially Increasing: Where are We in Recent Years?

2021 ◽  
Author(s):  
Umberto Galderisi ◽  
Gianfranco Peluso ◽  
Giovanni Di Bernardo
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Neurological Disorders ◽  
Therapeutic Approaches ◽  
Multipotent Stem Cells ◽  
Immune System Diseases ◽  
Differentiated Cells ◽  
New Therapeutic Approaches ◽  
Stromal Component

AbstractMesenchymal stromal cells (MSCs), present in the stromal component of several tissues, include multipotent stem cells, progenitors, and differentiated cells. MSCs have quickly attracted considerable attention in the clinical field for their regenerative properties and their ability to promote tissue homeostasis following injury. In recent years, MSCs mainly isolated from bone marrow, adipose tissue, and umbilical cord—have been utilized in hundreds of clinical trials for the treatment of various diseases. However, in addition to some successes, MSC-based therapies have experienced several failures. The number of new trials with MSCs is exponentially growing; still, complete results are only available for a limited number of trials. This dearth does not help prevent potentially inefficacious and unnecessary clinical trials. Results from unsuccessful studies may be useful in planning new therapeutic approaches to improve clinical outcomes. In order to bolster critical analysis of trial results, we reviewed the state of art of MSC clinical trials that have been published in the last six years. Most of the 416 published trials evaluated MSCs’ effectiveness in treating cardiovascular diseases, GvHD, and brain and neurological disorders, although some trials sought to treat immune system diseases and wounds and to restore tissue. We also report some unorthodox clinical trials that include unusual studies. Graphical abstract

scholarly journals Mechanistic approaches for the prevention and treatment of chronic GVHD

Blood ◽  
2017 ◽  
Vol 129 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Corey S. Cutler ◽  
John Koreth ◽  
Jerome Ritz
Keyword(s):  
Treatment Options ◽  
Chronic Gvhd ◽  
Therapeutic Approaches ◽  
Current Standard ◽  
New Agents ◽  
Hematopoietic Stem ◽  
New Therapeutic Approaches ◽  
Current Standard Treatment ◽  
Immune Pathology ◽  
Early Phase Clinical Trials

Abstract Clinical outcomes for patients undergoing allogeneic hematopoietic stem cell transplantation continue to improve, but chronic graft-versus-host disease (GVHD) remains a common toxicity and major cause of nonrelapse morbidity and mortality. Treatment of chronic GVHD has previously relied primarily on corticosteroids and other broadly immune suppressive agents. However, conventional immune suppressive agents have limited clinical efficacy in chronic GVHD, and prolonged immune suppressive treatments result in additional toxicities that further limit clinical recovery from transplant and return to normal daily function. Recent advances in our understanding of the immune pathology of chronic GVHD offer the possibility that new therapeutic approaches can be directed in more precise ways to target specific immunologic mechanisms and pathways. In this review, we briefly summarize current standard treatment options and present new therapeutic approaches that are supported by preclinical studies and early-phase clinical trials suggesting that these approaches may have clinical utility for treatment or prevention of chronic GVHD. Further evaluation of these new therapeutic options in well-designed prospective multicenter trials are needed to identify the most effective new agents and improve outcomes for patients with chronic GVHD.

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