Exploiting antibody biology for the treatment of cancer

Immunotherapy ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 255-267 ◽  
Author(s):  
Vidhi Khanna ◽  
Jayanth Panyam ◽  
Thomas S Griffith
Keyword(s):  
Antibody Therapy ◽  
Cancer Therapeutics ◽  
High Specificity ◽  
Mechanisms Of Action ◽  
Clinical Applications ◽  
Combination Therapies ◽  
Rational Combination ◽  
The Many ◽  
Key Aspects ◽  
Target Effects

Over the last decade, antibodies have become an important component in the arsenal of cancer therapeutics. High-specificity, low off-target effects, desirable pharmacokinetics and high success rate are a few of the many attributes that make antibodies amenable for development as drugs. To design antibodies for successful clinical applications, however, it is critical to have an understanding of their structure, functions, mechanisms of action and pharmacokinetic/pharmacodynamic properties. This review highlights some of these key aspects, as well as certain limitations encountered, with monoclonal antibody therapy. Further, we discuss rational combination therapies for clinical applications, some of which could help overcome the limitations.

scholarly journals HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3575
Author(s):  
Dimitris Karagiannis ◽  
Theodoros Rampias
Keyword(s):  
Tumor Heterogeneity ◽  
Histone Deacetylase Inhibitors ◽  
Phenotypic Variability ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Mechanisms Of Action ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
Environmental Selection ◽  
Stochastic Events

Intra-tumoral heterogeneity presents a major obstacle to cancer therapeutics, including conventional chemotherapy, immunotherapy, and targeted therapies. Stochastic events such as mutations, chromosomal aberrations, and epigenetic dysregulation, as well as micro-environmental selection pressures related to nutrient and oxygen availability, immune infiltration, and immunoediting processes can drive immense phenotypic variability in tumor cells. Here, we discuss how histone deacetylase inhibitors, a prominent class of epigenetic drugs, can be leveraged to counter tumor heterogeneity. We examine their effects on cellular processes that contribute to heterogeneity and provide insights on their mechanisms of action that could assist in the development of future therapeutic approaches.

scholarly journals A New Hope: Self-Assembling Peptides with Antimicrobial Activity

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 166 ◽  
Author(s):  
Lucia Lombardi ◽  
Annarita Falanga ◽  
Valentina Del Genio ◽  
Stefania Galdiero
Keyword(s):  
Self Assembly ◽  
Biomedical Applications ◽  
High Specificity ◽  
Antibacterial Activities ◽  
Mechanisms Of Action ◽  
Great Promise ◽  
Functional Nanomaterials ◽  
Self Assembling ◽  
Low Toxicity ◽  
Bio Compatibility

Peptide drugs hold great promise for the treatment of infectious diseases thanks to their novel mechanisms of action, low toxicity, high specificity, and ease of synthesis and modification. Naturally developing self-assembly in nature has inspired remarkable interest in self-assembly of peptides to functional nanomaterials. As a matter of fact, their structural, mechanical, and functional advantages, plus their high bio-compatibility and bio-degradability make them excellent candidates for facilitating biomedical applications. This review focuses on the self-assembly of peptides for the fabrication of antibacterial nanomaterials holding great interest for substituting antibiotics, with emphasis on strategies to achieve nano-architectures of self-assembly. The antibacterial activities achieved by these nanomaterials are also described.

scholarly journals Risks and risk management in modern multiple sclerosis immunotherapeutic treatment

2019 ◽  
Vol 12 ◽  
pp. 175628641983657 ◽  
Author(s):  
Luisa Klotz ◽  
Joachim Havla ◽  
Nicholas Schwab ◽  
Reinhard Hohlfeld ◽  
Michael Barnett ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Paradigm Shift ◽  
Mechanisms Of Action ◽  
Optimal Choice ◽  
New Drugs ◽  
Comprehensive Overview ◽  
Disease Modifying Drugs ◽  
Practical Recommendations ◽  
Target Effects

In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an ‘optimal choice’ for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations. Similarly, there are peculiarities and specific requirements with regard to treatment monitoring, especially in relation to immunosuppression, the development of secondary immune-related complications, as well as the existence of drug-specific on- and off-target effects. Both classical immunosuppression and selective immune interventions generate a spectrum of potential therapy-related complications. This article provides a comprehensive overview of available immunotherapeutics for MS and their risks, detailing individual mechanisms of action and side-effect profiles. Furthermore, practical recommendations for patients treated with modern MS immunotherapeutics are provided.

Enhanced external counterpulsation: mechanisms of action and clinical applications

2010 ◽  
Vol 65 (2) ◽  
pp. 239-247 ◽  
Author(s):  
V. Kitsou ◽  
T. Xanthos ◽  
R. Roberts ◽  
G.M. Karlis ◽  
L. Padadimitriou
Keyword(s):  
Mechanisms Of Action ◽  
Clinical Applications ◽  
External Counterpulsation ◽  
Enhanced External Counterpulsation

scholarly journals Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential

2007 ◽  
Vol 83 (980) ◽  
pp. 409-413 ◽  
Author(s):  
I. S Whitaker ◽  
C. Twine ◽  
M. J Whitaker ◽  
M. Welck ◽  
C. S Brown ◽  
...  
Keyword(s):  
Mechanisms Of Action ◽  
Clinical Applications ◽  
Future Potential ◽  
Larval Therapy

scholarly journals A scalable platform for the development of cell-type-specific viral drivers

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sinisa Hrvatin ◽  
Christopher P Tzeng ◽  
M Aurel Nagy ◽  
Hume Stroud ◽  
Charalampia Koutsioumpa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heterologous Gene Expression ◽  
High Specificity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Cell Type Specific ◽  
The Many ◽  
Dna Regulatory Elements

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.

scholarly journals Fucoxanthin induced apoptotic cell death in oral squamous carcinoma (KB) cells

2021 ◽  
Vol 17 (1) ◽  
pp. 181-191
Author(s):  
Petchi Iyappan ◽  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Biological Activities ◽  
Squamous Carcinoma ◽  
Cancer Therapeutics ◽  
Kb Cells ◽  
Oral Squamous Carcinoma ◽  
The Many

Fucoxanthin (Fx) is an active compound commonly found in the many types of seaweed with numerous biological activities. The main goal of this investigation is to explore the effect of Fx against the cell proliferation, apoptotic induction and oxidative stress in the oral squamous (KB) cell line. Cytotoxicity of Fx was determined by MTT assay. The intracellular ROS production, mitochondrial membrane potential (MMP) and apoptosis induction in KB cells were examined through DCFH-DA, Rhodamine-123 and DAPI, and dual staining techniques. Effect of Fx on the antioxidant enzymes and lipid peroxidation in the KB cells was studied through the standard procedures. Fx treated KB cells showed morphological changes and reduced cell survival, which is exhibited by the cytotoxic activity of 50 μM/ml (IC50) Fx against the KB cells. The Fx treatment considerably induced the apoptotosis cells (EB/AO) and decreased the MMP (Rh-123) in KB cells. Further, it was pointed out that there was an increased lipid peroxidation (LPO) with decreased antioxidants (CAT, SOD and GSH). These results concluded that Fx has the cytotoxic effect against KB cells and has the potential to induce the apoptosis via increased oxidative stress. Hence, the Fx can be a promising agent for the treatment of oral cancer and it may lead to the development of cancer therapeutics.

scholarly journals Antigen-Specific Immune Tolerance in Multiple Sclerosis—Promising Approaches and How to Bring Them to Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreas Lutterotti ◽  
Helen Hayward-Koennecke ◽  
Mireia Sospedra ◽  
Roland Martin
Keyword(s):  
Multiple Sclerosis ◽  
Patient Selection ◽  
Tolerance Induction ◽  
Mechanisms Of Action ◽  
Clinical Development ◽  
Clinical Testing ◽  
Development Path ◽  
Conventional Drug ◽  
Key Aspects ◽  
Specific Tolerance

Antigen-specific tolerance induction aims at treating multiple sclerosis (MS) at the root of its pathogenesis and has the prospect of personalization. Several promising tolerization approaches using different technologies and modes of action have already advanced to clinical testing. The prerequisites for successful tolerance induction include the knowledge of target antigens, core pathomechanisms, and how to pursue a clinical development path that is distinct from conventional drug development. Key aspects including patient selection, outcome measures, demonstrating the mechanisms of action as well as the positioning in the rapidly growing spectrum of MS treatments have to be considered to bring this therapy to patients.

scholarly journals Monoclonal Antibody Therapy and Long-term Outcomes in Multiple Sclerosis – The Challenge of Treatment Optimisation

2018 ◽  
Vol 13 (2) ◽  
pp. 78
Author(s):  
Antonio Scalfari ◽  
Paolo A Muraro ◽  
◽  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Antibody Therapy ◽  
Careful Consideration ◽  
Therapeutic Landscape ◽  
Treatment Optimisation ◽  
Frequent Administration ◽  
Therapeutic Opportunity ◽  
The Many ◽  
The Cost

The therapeutic landscape of multiple sclerosis (MS) has been transformed by the advent of several new monoclonal antibody (MAb) therapies that can potentially lead to full stabilisation of detectable disease activity. Natalizumab, alemtuzumab and ocrelizumab are currently licensed MAbs for the treatment of MS. Daclizumab was licensed for the treatment of MS, although it has been recently withdrawn from the market by the manufacturer. Most patients are initially managed with first-line treatments, and, if disease breakthrough occurs, are escalated to a stronger compound, yet the available evidence indicates an early window of therapeutic opportunity for MAbs to exert most of their efficacy. It is important to balance the superior efficacy of MAbs compared with injectable treatments against more serious side effects, although these are well recognised and can be monitored where indicated and treated. In particular, the risk of progressive multifocal leucoencephalopathy with natalizumab can be managed by screening potential patients for the John Cunningham virus. The MAbs also have the benefit of convenience to patients compared with daily or weekly treatments since they are given via less frequent administration. The cost of these treatments, compared with other therapies, may be an important issue in many countries where healthcare budgets are under pressure. The complex decision of choosing the best treatment for an individual should be made jointly between the doctor and the patient after careful consideration of the many factors to be weighed.

scholarly journals Multiomics analysis of serial PARP inhibitor treated metastatic TNBC inform on rational combination therapies

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marilyne Labrie ◽  
Allen Li ◽  
Allison Creason ◽  
Courtney Betts ◽  
Jamie Keck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Patient Specific ◽  
Combination Therapies ◽  
Breast Cancer Patients ◽  
Effector Cells ◽  
Basal Breast Cancer ◽  
Rational Combination

AbstractIn a pilot study, we evaluated the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). In a BRCA-mutant basal breast cancer exceptional long-term survivor, a striking tumor destruction was accompanied by a marked infiltration of immune cells containing CD8 effector cells, consistent with pre-clinical evidence for association between STING mediated immune activation and benefit from PARPi and immunotherapy. Tumor cells in the exceptional responder underwent extensive protein network rewiring in response to PARP inhibition. In contrast, there were minimal changes in the ecosystem of a luminal androgen receptor rapid progressor, likely due to indifference to the effects of PARP inhibition. Together, identification of PARPi-induced emergent changes could be used to select patient specific combination therapies, based on tumor and immune state changes.

Sign in / Sign up

Export Citation Format

Share Document