COVID-19 vaccine race: watch your step for cancer patients.
TL;DR: A careful evaluation of the efficacy of these promising mRNA COVID-19 vaccines administered as lipid carriers for patients with solid tumours is needed, including a possible re-appraisal of the dosing for optimal protection of this specific and frail population.
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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TL;DR: A computational study demonstrates 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 be considered a conceptual background for the development of miRNA-based drugs against COVID-19.
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.
28 citations
Cites background or methods from "COVID-19 vaccine race: watch your s..."
...Moreover, to favor their administration in humans and to increase their availability and overall, their efficiency, LNA-based oligosequences are encapsulated into liposomes and delivered as lipid nanoparticles [80,81]....
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...This modification and administration have been successfully used for mRNA-based vaccines that reach phase trials with promising efficacy [80]....
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TL;DR: Based on a review of the available data on the efficacy and safety of the approved and forthcoming vaccines in patients with cancer, the authors recommended that most patients should receive the recommended dose and schedule of one of the COVID-19 vaccines when available.
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
17 citations
TL;DR: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted, and active cancer treatment had little impact on adverse event profiles.
Abstract: BACKGROUND
Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy.
PATIENTS AND METHODS
A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose.
RESULTS
The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment.
CONCLUSIONS
When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.
14 citations
TL;DR: In this paper, the authors discuss the current recommendations for use of COVID-19 vaccination in patients with cancer and discuss the concerns of efficacy due to the variable immune response in patients undergoing active cancers undergoing active therapy and cancer survivors with chronic immunosuppression.
Abstract: While emergency use is authorized for numerous COVID-19 vaccines and the high-risk population including cancer patients or those with immunosuppression due to disease or therapy is prioritized, data on this group’s specific safety and efficacy of these vaccines remains limited. Safety data from clinical trials and population data may be extrapolated, and these vaccines may be used for cancer patients. However, concerns of efficacy due to the variable immune response in patients with active cancers undergoing active therapy and cancer survivors with chronic immunosuppression remain. The authors aim to discuss the current recommendations for use of COVID-19 vaccination in patients with cancer.
10 citations
References
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TL;DR: 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.
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.
1,515 citations
TL;DR: 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.
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.
1,140 citations
TL;DR: The EPR-effect appears as a universal phenomenon in solid tumors which warrants the development of other polymeric drugs or nanomedicine, and then advantages and problems of macromolecular drugs.
1,081 citations
"COVID-19 vaccine race: watch your s..." refers background in this paper
...Reduced lymphatic drainage further explains why nanoparticles will accumulate in the tumour micro-environment after leaking out of the blood vessels.(6) Experimental data in tumour-bearing animals have already shown how the EPR effect was dependent on liposome size, i....
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TL;DR: It is demonstrated that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins.
554 citations
TL;DR: This comprehensive review discusses the impact of COVID-19 on health and the immune system of those affected, reviewing the latest treatment approaches and ongoing clinical trials and proposes potential approaches to manage this vulnerable population during this pandemic.
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.
220 citations