scholarly journals Concepts in Oncolytic Adenovirus Therapy

2021 ◽  
Vol 22 (19) ◽  
pp. 10522
Author(s):  
Klaus Mantwill ◽  
Florian Gerhard Klein ◽  
Dongbiao Wang ◽  
Sruthi Vasantamadhava Hindupur ◽  
Maximilian Ehrenfeld ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Adenovirus Vector ◽  
Adenoviral Vectors ◽  
Tumour Cells ◽  
Oncolytic Adenovirus ◽  
Genetic Manipulations ◽  
Novel Treatment ◽  
Adenovirus Vectors ◽  
Anti Tumour Effect

Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors allow for genetic manipulations that restrict tumour specificity and also the expression of specific transgenes in order to support the anti-tumour effect. Additionally, replication of the virus and reinfection of neighbouring tumour cells amplify the therapeutic effect. Another important aspect in oncolytic adenovirus therapy is the virus induced cell death which is a process that activates the immune system against the tumour. This review describes which elements in adenovirus vectors have been identified for modification not only to utilize oncolytic adenovirus vectors into conditionally replicating adenoviruses (CRAds) that allow replication specifically in tumour cells but also to confer specific characteristics to these viruses. These advances in development resulted in clinical trials that are summarized based on the conceptual design.

scholarly journals COMPARES mRNA AND ADENOVIRUS-BASED SARS-CoV-2 VACCINES

2021 ◽  
pp. 77-82
Author(s):  
HISA FAADHILAH ◽  
KARINA O. WISEVA ◽  
FRIDA WIDYASTUTI ◽  
NASRUL WATHONI
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Adenovirus Vector ◽  
Advantages And Disadvantages ◽  
Adenovirus Vectors ◽  
Different Doses

This review is aimed at looking at the Covid-19 vaccine, formula and comparison of mRNA (Moderna and Pfizer) and adenovirus vector (AstraZeneca) vaccines that have been circulating in terms of administration, effectiveness, safety, side effects, contraindications, and in terms of price. This review was conducted by taking some literature from a database that focuses on the Covid vaccine, the development of the Covid vaccine, the Moderna vaccine, the Pfizer vaccine, and the AstraZeneca vaccine. Three vaccines, 2 were mRNA-based vaccines (Moderna and Pfizer) and 1, namely AstraZeneca, was based on adenovirus vectors. The results obtained are from international journals with the keyword comparison of mRNA vaccine and adenovirus vector, then the results show that the comparison can be seen through the method carried out. Some vaccines have their own advantages and disadvantages. When viewed from several aspects, such as administration which has different doses. Then seen from the effectiveness of the three vaccines have a sufficient value because they are above 80%. For safety, it has passed clinical trials in humans, but there are still shortcomings in each vaccine of course. Vaccines derived from mRNA (Moderna) are the most expensive vaccines because of the highest safety.

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

scholarly journals Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1128
Author(s):  
Amy Kwan ◽  
Natalie Winder ◽  
Munitta Muthana
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Menopausal Status ◽  
Oncolytic Virotherapy ◽  
Immunogenic Cell Death ◽  
Tumour Type ◽  
Common Cancer ◽  
Direct Cell

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

scholarly journals Simian adenovirus vector production for early-phase clinical trials: A simple method applicable to multiple serotypes and using entirely disposable product-contact components

Vaccine ◽  
2019 ◽  
Vol 37 (47) ◽  
pp. 6951-6961 ◽  
Author(s):  
Sofiya Fedosyuk ◽  
Thomas Merritt ◽  
Marco Polo Peralta-Alvarez ◽  
Susan J Morris ◽  
Ada Lam ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Adenovirus Vector ◽  
Simple Method ◽  
Simian Adenovirus ◽  
Early Phase Clinical Trials

scholarly journals Targeting Sphingolipids for Cancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Osmel Companioni ◽  
Cristina Mir ◽  
Yoelsis Garcia-Mayea ◽  
Matilde E. LLeonart
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Cancer Therapy ◽  
Preclinical Studies ◽  
Hepatic Toxicity ◽  
Multiple Cancers ◽  
Extensive Class ◽  
Effective Drugs

Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. Sphingolipids are modified in multiple cancers and are responsible for tumor proliferation, progression, and metastasis. Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo. As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. The most effective drugs are fenretinide and α-galactosylceramide (α-GalCer). In contrast, minor adverse effects restricted to a few subjects and hepatic toxicity have been observed in clinical trials of ABC294640 and safingol, respectively. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review.

scholarly journals Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism

2018 ◽  
Vol 7 (5) ◽  
pp. R196-R211 ◽  
Author(s):  
Jaafar Jaafar ◽  
Eugenio Fernandez ◽  
Heba Alwan ◽  
Jacques Philippe
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
English Language ◽  
Case Series ◽  
Immune Checkpoints ◽  
Pubmed Database ◽  
Programmed Cell Death 1 ◽  
Time To Onset

Background Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs). Purpose We review the incidence, time to onset and resolution rate of dysthyroidism induced by PD-1/PD-L1 Ab, and the clinical, biological and radiological findings. We aim to discuss the potential mechanisms of PD-1/PD-L1 Ab-induced dysthyroidism, and to propose a management algorithm. Methods We performed a literature search of available clinical trials regarding PD-1/PD-L1 Ab in the PubMed database. We selected all English language clinical trials that included at least 100 patients. We also present selected case series or reports, retrospective studies and reviews related to this issue. Findings In patients treated with PD-1 Ab, hypothyroidism occurred in 2–10.1% and hyperthyroidism occurred in 0.9–7.8%. When thyroiditis was reported separately, it occurred in 0.34–2.6%. Higher rates were reported when PD-1 Ab were associated with other ICI or chemotherapy. The median time to onset of hyperthyroidism and hypothyroidism after PD-1 Ab initiation was 23–45 days and 2–3.5 months, respectively. Regarding PD-L1 Ab, hypothyroidism occurred in 0–10% and hyperthyroidism in 0.5–2% of treated patients. The average time to onset of dysthyroidism after PD-L1 Ab was variable and ranged from 1 day after treatment initiation to 31 months. Conclusion Dysthyroidism occurs in up to 10% of patients treated with PD-1/PD-L1 Ab. Hypothyroidism and reversible destructive thyroiditis are the most frequent endocrine adverse events (eAE) in PD-1/PD-L1 treated patients. Immune and non-immune mechanisms are potentially involved, independently of the presence of thyroid antibodies.

scholarly journals Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2761
Author(s):  
Fabiana Mallone ◽  
Marta Sacchetti ◽  
Alessandro Lambiase ◽  
Antonietta Moramarco
Keyword(s):  
Clinical Trials ◽  
Uveal Melanoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Metastatic Tumor ◽  
Clinical Use ◽  
Future Perspectives ◽  
Diagnosis And Prognosis ◽  
Novel Treatment ◽  
Combinational Therapies

Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

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