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Open accessJournal ArticleDOI: 10.1038/S41416-020-01219-3

COVID-19 vaccine race: watch your step for cancer patients.

02 Mar 2021-British Journal of Cancer (Nature Publishing Group)-Vol. 124, Iss: 5, pp 860-861
Abstract: Patients with cancer should benefit from COVID-19 vaccination. Some of the most advanced vaccine candidates are mRNAs encapsulated into lipid carriers, and small liposomes are expected to accumulate in tumour tissues through the enhanced and permeation retention effect. However, to what extent solid tumours could take up a significant part of the vaccine dose as well remains unknown. This calls for a careful evaluation of the efficacy of these promising mRNA COVID-19 vaccines administered as lipid carriers for patients with solid tumours, including a possible re-appraisal of the dosing for optimal protection of this specific and frail population.

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Topics: Vaccination (53%), Population (52%)
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14 results found


Open accessJournal ArticleDOI: 10.3390/NCRNA7010014
Lucia Natarelli1, Luca Parca2, Tommaso Mazza2, Christian Weber  +2 moreInstitutions (3)
18 Feb 2021-Non-Coding RNA
Abstract: The respiratory system is one of the most affected targets of SARS-CoV-2. Various therapies have been utilized to counter viral-induced inflammatory complications, with diverse success rates. Pending the distribution of an effective vaccine to the whole population and the achievement of "herd immunity", the discovery of novel specific therapies is to be considered a very important objective. Here, we report a computational study demonstrating the existence of target motifs in the SARS-CoV-2 genome suitable for specific binding with endogenous human micro and long non-coding RNAs (miRNAs and lncRNAs, respectively), which can, therefore, be considered a conceptual background for the development of miRNA-based drugs against COVID-19. The SARS-CoV-2 genome contains three motifs in the 5'UTR leader sequence recognized by selective nucleotides within the seed sequence of specific human miRNAs. The seed of 57 microRNAs contained a "GGG" motif that promoted leader sequence-recognition, primarily through offset-6mer sites able to promote microRNAs noncanonical binding to viral RNA. Similarly, lncRNA H19 binds to the 5'UTR of the viral genome and, more specifically, to the transcript of the viral gene Spike, which has a pivotal role in viral infection. Notably, some of the non-coding RNAs identified in our study as candidates for inhibiting SARS-CoV-2 gene expression have already been proposed against diverse viral infections, pulmonary arterial hypertension, and related diseases.

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Topics: Population (52%), Genome (51%), microRNA (50%)

12 Citations



Journal ArticleDOI: 10.1080/07357907.2021.1885596
Abstract: Given the rapidly expanding global spread of the SARS-Co-V-2 virus and the expanding number of individuals with the serious and potentially fatal illness, COVID-19, there is an urgent need for safe and effective vaccines Based on compelling evidence that patients with cancer are at increased risk for greater morbidity and mortality with COVID-19, several professional organizations have provided early guidance on the role of COVID-19 vaccines in patients with malignant disease In this commentary we review the available data on the efficacy and safety of the approved and forthcoming vaccines in patients with cancer Based on a review of the totality of available evidence, we recommend that most patients with cancer should receive the recommended dose and schedule of one of the COVID-19 vaccines when available We encourage industry, regulators and professional research organizations to carefully track the efficacy and safety of COVID-19 vaccination in patients with cancer in the real world setting and routinely report unanticipated adverse events and signs of loss of efficacy Particular attention is needed for patients on active cancer therapy to carefully evaluate efficacy and safety in relationship to the timing of vaccination relative to that of active cancer treatment and immunosuppression

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Topics: Cancer (50%)

6 Citations


Open accessPosted ContentDOI: 10.1101/2020.12.21.20248608
Annika Fendler1, Lewis Au1, Lewis Au2, Laura Amanda Boos2  +70 moreInstitutions (6)
23 Dec 2020-medRxiv
Abstract: SUMMARY There is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer patients and inform risk-reduction strategies and preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. SARS-CoV-2-specific T-cell responses were detected, and CD4+ T-cell responses correlated with S1 antibody levels. Patients with haematological malignancies had impaired but partially compensated immune responses. Overall, cancer stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in the cancer population.

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Topics: Cancer (57%), Population (51%)

4 Citations


Journal ArticleDOI: 10.1080/14760584.2021.1951246
Abstract: Introduction The discovery of neoantigens as mutated proteins specifically expressed in tumor cells but not in normal cells has led to improved cancer vaccines. Targeting neoantigens can induce anti-tumor T-cell responses to destroy tumors without damaging healthy cells. Extensive advances in genome sequencing technology and bioinformatics analysis have made it possible to discover and design effective neoantigens for use in therapeutic cancer vaccines. Neoantigens-based therapeutic personalized vaccines have shown promising results in cancer immunotherapy. Areas covered We discuss the types of cancer neoantigens that can be recognized by the immune system in this review. We also summarize the detection, identification, and design of neoantigens and their appliction in developing cancer vaccines. Finally, clinical trials of neoantigen-based vaccines, their advantages, and their limitations are reviewed. From 2015 to 2020, the authors conducted a literature search of controlled randomized trials and laboratory investigations that that focused on neoantigens, their use in the design of various types of cancer vaccines. Expert opinion Neoantigens are cancer cell-specific antigens, which their expression leads to the immune stimulation against tumor cells. The identification and delivery of specific neoantigens to antigen-presenting cells (APCs) with the help of anti-cancer vaccines promise novel and more effective cancer treatments.

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Topics: Cancer immunotherapy (52%)

1 Citations


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11 results found


Journal ArticleDOI: 10.1016/J.EJPB.2008.11.010
Abstract: For over half a century extensive research has been undertaken for the control of cancer. However, success has been limited to certain malignancies, and surgical intervention is potentially curative for early stage patients. For the majority of patients with advanced stage of cancer, the treatment is limited to chemotherapy or radiation. Chemotherapy in particular has limitations due to the lack of selectivity with severe toxicity. Under these circumstances tumor-targeted delivery of anticancer drugs is perhaps one of the most important steps for cancer chemotherapy. We reported such a drug for the first time, styrene-maleic acid copolymer-conjugated neocarzinostatin (SMANCS) in 1979, and it eventually led to formulate the concept of the enhanced permeability and retention (EPR) effect of solid tumors in 1986. Monoclonal antibody conjugates are another direction, of which interest is increasing recently though with limited success. The EPR-effect appears as a universal phenomenon in solid tumors which warrants the development of other polymeric drugs or nanomedicine. EPR-effect is applicable for any biocompatible macromolecular compounds above 40 kDa, even larger than 800 kDa, or of the size of bacteria; thus complexed molecules like micelles and liposomes containing anticancer drugs are hallmark examples. The drug concentration in tumor compared to that of the blood (T/B ratio) can be usually as high as 10-30 times. In case of SMANCS/Lipiodol given via tumor feeding artery, the T/B ratio can be as high as 2000, a real pin-point targeting. EPR-effect is not just passive targeting for momentary tumor delivery, but it means prolonged drug retention for more than several weeks or longer. This review describes the pathophysiological mechanisms of the EPR-effect, architectural difference of tumor blood vessel, various factors involved and artificial augmentation of EPR-effect with respect to tumor-selective delivery, and then advantages and problems of macromolecular drugs.

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Topics: Targeted drug delivery (60%), Drug delivery (56%), Polymer-drug conjugates (54%) ... read more

1,032 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2798-3
Florian Krammer1Institutions (1)
23 Sep 2020-Nature
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years. The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.

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Topics: Viral Vaccine (52%)

790 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2639-4
22 Oct 2020-Nature
Abstract: In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.

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Topics: Vaccination (56%), Reactogenicity (54%), Immunogenicity (51%)

664 Citations


Open accessJournal ArticleDOI: 10.1016/J.JCONREL.2015.08.007
Abstract: In recent years, in vitro transcribed messenger RNA (mRNA) has emerged as a potential therapeutic platform To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clinical trials However, little is known about the potential of LNPs to deliver mRNA Here, we generated mRNA-LNPs by incorporating HPLC purified, 1-methylpseudouridine-containing mRNA comprising codon-optimized firefly luciferase into stable LNPs Mice were injected with 0005-0250mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging Subcutaneous, intramuscular and intradermal injection of the LNP-encapsulated mRNA translated locally at the site of injection for up to 10days For several days, high levels of protein production could be achieved in the lung from the intratracheal administration of mRNA Intravenous and intraperitoneal and to a lesser extent intramuscular and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins

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305 Citations


Open accessJournal ArticleDOI: 10.1007/S11912-020-00934-7
Rohit Gosain1, Yara Abdou1, Abhay Singh1, Navpreet Rana2  +2 moreInstitutions (2)
Abstract: The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged to be the biggest global health threat worldwide, which has now infected over 1.7 million people and claimed more than 100,000 lives around the world. Under these unprecedented circumstances, there are no well-established guidelines for cancer patients. The risk for serious disease and death in COVID-19 cases increases with advancing age and presence of comorbid health conditions. Since the emergence of the first case in Wuhan, China, in December 2019, tremendous research efforts have been underway to understand the mechanisms of infectivity and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a fatal virus responsible for abysmal survival outcomes. To minimize the mortality rate, it becomes prudent to identify symptoms promptly and employ treatments appropriately. Even though no cure has been established, multiple clinical trials are underway to determine the most optimal strategy. Managing cancer patients under these circumstances is rather challenging, given their vulnerable status and the aggressive nature of their underlying disease. In this comprehensive review, we discuss the impact of COVID-19 on health and the immune system of those affected, reviewing the latest treatment approaches and ongoing clinical trials. Additionally, we discuss challenges faced while treating cancer patients and propose potential approaches to manage this vulnerable population during this pandemic.

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Topics: Global health (54%), Disease (51%)

140 Citations


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