-
International Journal of Molecular... May 2021Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic... (Review)
Review
Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.
Topics: Animals; Antibodies; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Apolipoproteins B; Atherosclerosis; Autoantibodies; Cardiovascular Diseases; Cholesterol, LDL; Cytokines; Humans; Immunization, Passive; Inflammation; Peptide Fragments; Proprotein Convertase 9; Stroke
PubMed: 34071276
DOI: 10.3390/ijms22115770 -
Biomedicine & Pharmacotherapy =... Jun 2023Immune checkpoint inhibitor (ICI) resistance demands for acquisition of novel strategies in order to broaden the therapeutic repertoire of advanced cancers. Bispecific... (Review)
Review
Immune checkpoint inhibitor (ICI) resistance demands for acquisition of novel strategies in order to broaden the therapeutic repertoire of advanced cancers. Bispecific antibodies can be utilized as an emerging therapeutic paradigm and a step forward in cancer immunotherapy. Synchronous inhibition of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte associated antigen-4 (CTLA-4), or with other agents can expand antibody selectivity and improve therapeutic window through tightening cell-to-cell bridge (a process called immunological synapse) within tumor immune microenvironment (TIME). There is evidence of higher potency of this co-targeting approach over combined single-agent monoclonal antibodies in reinvigorating anti-tumor immune responses, retarding tumor growth, and improving patient survival. In fact, immunological synapses formed by interactions of such bispecific agents with TIME cells directly mediate cytotoxicity against tumor cells, and durable anti-tumor immune responses are predictable after application of such agents. Besides, lower adverse events are reported for bispecific antibodies compared with individual checkpoint inhibitors. These are all indicative of the importance of exploiting novel bispecific approach as a replacement for conventional combo checkpoint inhibitor therapy particularly for tumors with immunosuppressive or cold immunity. Study in this area is still continued, and in the future more will be known about the importance of this bispecific approach in cancer immunotherapy.
Topics: Humans; Antibodies, Bispecific; Neoplasms; Antibodies, Monoclonal; Immunotherapy; Tumor Microenvironment
PubMed: 37004328
DOI: 10.1016/j.biopha.2023.114621 -
Viruses Jul 2023This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics... (Review)
Review
This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, , . The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.
Topics: Humans; Immunoglobulins; Globulins; Immunization, Passive; Vaccines; Communicable Diseases; Antibodies, Viral
PubMed: 37515229
DOI: 10.3390/v15071543 -
Med (New York, N.Y.) Feb 2023With the increasing use of antibody therapeutics, clinicians are faced with challenges of precisely stratifying patients and promptly assessing response to treatment....
With the increasing use of antibody therapeutics, clinicians are faced with challenges of precisely stratifying patients and promptly assessing response to treatment. Antibody theranostics combines the advantages of radionuclides and antibodies (or antibody derivatives) to systematically integrate targeted diagnostics and therapeutics and will play important roles in precision medicine.
Topics: Humans; Precision Medicine; Antibodies; Radioisotopes
PubMed: 36724783
DOI: 10.1016/j.medj.2023.01.001 -
American Journal of Hematology Mar 2023Immune therapies, including CAR-T cells, bispecific antibodies, and antibody-drug conjugates, are revolutionizing the treatment of multiple myeloma. In this review, we... (Review)
Review
Immune therapies, including CAR-T cells, bispecific antibodies, and antibody-drug conjugates, are revolutionizing the treatment of multiple myeloma. In this review, we discuss clinical trial design considerations relevant to immune therapies. We first examine issues pertinent to specific populations, including elderly, patients with renal impairment, high-risk/extramedullary disease, and prior immune therapies. We then highlight trial designs to optimize the selection of dose and schedule, explore rational combination therapies based on preclinical data, and evaluate the nuances of commonly used endpoints. By exploiting their pharmacokinetic/pharmacodynamic profiles and utilizing novel translational insights, we can optimize the use of immune therapies in multiple myeloma.
Topics: Humans; Aged; Multiple Myeloma; Antibodies, Bispecific; Immunoconjugates; Immunotherapy, Adoptive; Combined Modality Therapy
PubMed: 36200130
DOI: 10.1002/ajh.26753 -
International Journal of Molecular... Sep 2021Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices... (Review)
Review
Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices continue to substantially contribute to the fight against cancer. However, these practices do have some risks, adverse effects and limitations, which can affect patient outcomes. Although antibodies have been developed, successfully used and proven beneficial in various oncology practices, the use of antibodies also comes with certain challenges and limitations (large in size, poor tumor penetration, high immunogenicity and a long half-life). Therefore, it is vital to develop new ways to visualize, diagnose and treat cancer. Nanobodies are novel antigen-binding fragments that possess many advantageous properties (small in size, low immunogenicity and a short half-life). Thus, the use of nanobodies in cancer practices may overcome the challenges experienced with using traditional antibodies. In this review, we discuss (1) the challenges with antibody usage and the superior qualities of nanobodies; (2) the use of antibodies and nanobodies in cancer imaging, diagnosis, drug delivery and therapy (surgery, radiotherapy, chemotherapy and immunotherapy); and (3) the potential improvements in oncology practices due to the use of nanobodies as compared to antibodies.
Topics: Antibodies; Drug Delivery Systems; Humans; Immunotherapy; Neoplasms; Single-Domain Antibodies
PubMed: 34575943
DOI: 10.3390/ijms22189778 -
Biomolecules Jun 2020Mesothelin (MSLN) is a cell surface glycoprotein normally expressed only on serosal surfaces, and not found in the parenchyma of vital organs. Many solid tumors also... (Review)
Review
Mesothelin (MSLN) is a cell surface glycoprotein normally expressed only on serosal surfaces, and not found in the parenchyma of vital organs. Many solid tumors also express MSLN, including mesothelioma and pancreatic adenocarcinoma. Due to this favorable expression profile, MSLN represents a viable target for directed anti-neoplastic therapies, such as recombinant immunotoxins (iToxs). Pre-clinical testing of MSLN-targeted iTox's has yielded a strong body of evidence for activity against a number of solid tumors. This has led to multiple clinical trials, testing the safety and efficacy of the clinical leads SS1P and LMB-100. While promising clinical results have been observed, neutralizing anti-drug antibody (ADA) formation presents a major challenge to overcome in the therapeutic development process. Additionally, on-target, off-tumor toxicity from serositis and non-specific capillary leak syndrome (CLS) also limits the dose, and therefore, impact anti-tumor activity. This review summarizes existing pre-clinical and clinical data on MSLN-targeted iTox's. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Clinical Trials as Topic; GPI-Linked Proteins; Gene Expression Regulation; Humans; Immunoconjugates; Immunotoxins; Mesothelin; Mesothelioma; Molecular Targeted Therapy; Pancreatic Neoplasms
PubMed: 32605175
DOI: 10.3390/biom10070973 -
Expert Review of Anticancer Therapy 2015Melanoma patients develop resistance to most therapies, including chemo- and targeted-therapy drugs. Single-agent therapies are ineffective due to the heterogeneous... (Review)
Review
Melanoma patients develop resistance to most therapies, including chemo- and targeted-therapy drugs. Single-agent therapies are ineffective due to the heterogeneous nature of tumors comprising several subpopulations. Treatment of melanoma with immune-based therapies such as anti-cytotoxic T-lymphocyte activation-4 and anti-programmed death-1 antibodies has shown modest but long-lasting responses. Unfortunately, only subsets of melanoma patients respond to antibody-based therapies. Heterogeneity in lymphocyte infiltration and low frequency of anti-melanoma-reactive T-cells in tumor lesions are partly responsible for a lack of response to antibody-based therapies. Both antibodies have same biological function but they bind to different ligands at various phases of T-cell activity. Thus, combination therapy of antibodies has shown superior response rates than single-agent therapy. However, toxicity is a cause of concern in these therapies. Future identification of therapy-response biomarkers, mobilization of tumor-reactive T-cell infiltration using cancer vaccines, or non-specific targeted-therapy drugs will minimize toxicity levels and provide long-term remissions in melanoma patients.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Resistance, Neoplasm; Humans; Ipilimumab; Melanoma; Molecular Targeted Therapy; Nivolumab; Skin Neoplasms
PubMed: 26402246
DOI: 10.1586/14737140.2015.1093418 -
Human Vaccines & Immunotherapeutics Aug 2023Monoclonal antibody-based targeted therapies have greatly improved treatment options for patients by binding to the innate immune system. However, the long-term efficacy... (Review)
Review
Monoclonal antibody-based targeted therapies have greatly improved treatment options for patients by binding to the innate immune system. However, the long-term efficacy of such antibodies is limited by mechanisms of drug resistance. Over the last 50 years, with advances in protein engineering technology, more and more bispecific antibody (bsAb) platforms have been engineered to meet diverse clinical needs. Bispecific NK cell engagers (BiKEs) or tri-specific NK cell engagers (TriKEs) allow for direct targeting of immune cells to tumors, and therefore resistance and serious adverse effects are greatly reduced. Many preclinical and clinical trials are currently underway, depicting the promise of antibody-based natural killer cell engager therapeutics. In this review, we compile worldwide efforts to explore the involvement of NK cells in bispecific antibodies. With a particular emphasis on lessons learned, we focus on preclinical and clinical studies in malignancies and discuss the reasons for the limited success of NK-cell engagers against solid tumors, offering plausible new ideas for curing some advanced cancers shortly.
Topics: Humans; Antibodies, Bispecific; Neoplasms; Killer Cells, Natural; Immunotherapy, Adoptive; Immunotherapy
PubMed: 37772505
DOI: 10.1080/21645515.2023.2256904 -
Current Opinion in Infectious Diseases Jun 2019This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of... (Review)
Review
PURPOSE OF REVIEW
This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of current clinical trials.
RECENT FINDINGS
Monoclonal antibody (mAb) therapy is becoming increasingly promising in the infectious disease field. Though bacterial exotoxins continue to be a mainstay of mAb targets, searches for protein targets on the surface of bacteria have uncovered new mechanisms of antibody-mediated action against bacteria. Additionally, surveys of the polysaccharide serotype prevalence among antibiotic-resistant bacterial populations have yielded opportunities to leverage human selective pressures to our clinical advantage. Several mAb candidates are progressing through clinical development with great promise, especially those with structures altered to provide maximum benefit. Although other clinical trials have recently proved unsuccessful, these failures and lessons from immune profiling provide opportunities to understand how vulnerabilities of certain targets may change in different disease states.
SUMMARY
Despite the hurdles of identifying effective targets and understanding how mAbs provide protection within different infections, we show that the progress made in these fields is a positive indication of mAbs becoming more widely accepted as the future for treating bacterial infections.
Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Bacterial Infections; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Immunotherapy
PubMed: 30950853
DOI: 10.1097/QCO.0000000000000539