scholarly journals Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy

2021 ◽  
Author(s):  
Rachna T Shroff ◽  
Pavani Chalasani ◽  
Ran Wei ◽  
Daniel Pennington ◽  
Grace Quirk ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Immune Responses ◽  
Cancer Patients ◽  
Neutralizing Antibodies ◽  
Fold Increase ◽  
Control Cohort ◽  
Tumor Patients ◽  
Specific Memory ◽  
Anti Cancer ◽  
B Cell Subsets

Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We evaluated immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=52) on active cytotoxic anti-cancer therapy. These responses were compared to a control cohort that also received the Pfizer/BioNTech vaccine (n=50). Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFN𝛾+ Spike-specific T cells. The magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD- and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to viral exposures or additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. These data suggest that a third immunization might elevate antibody responses in cancer patients to levels seen in healthy individuals after the second dose. Trials should be conducted to test these predictions.

scholarly journals Do checkpoint inhibitors compromise the cancer patients’ immunity and increase the vulnerability to COVID-19 infection?

Immunotherapy ◽  
2020 ◽  
Author(s):  
Joseph Kattan ◽  
Clarisse Kattan ◽  
Tarek Assi
Keyword(s):  
Cancer Therapy ◽  
Severe Acute Respiratory Syndrome ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Outcomes ◽  
Toxicity Profile ◽  
Anti Cancer ◽  
Acquired Immunodeficiency ◽  
Improvement In Survival

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has been declared a pandemic by the WHO that claimed the lives of thousands of people within a few months. Cancer patients represent a vulnerable population due to the acquired immunodeficiency associated with anti-cancer therapy. Immune checkpoint inhibitors have largely impacted the prognosis of a multitude of malignancies with significant improvement in survival outcomes and a different, tolerable toxicity profile. In this paper, we assess the safety of ICI administration in cancer patients during the coronavirus pandemic in order to guide the usage of these highly efficacious agents.

Analysis of Spontaneous Vs. Vaccine-Induced Antibody Responses Against Cancer-Testis Antigen MAGE-A3 in Cancer Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5087-5087
Author(s):  
Yanran Cao ◽  
Sacha Gnjatic ◽  
Vincent G. Brichard ◽  
Tim Luetkens ◽  
Sebastian Kobold ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Specific Antibodies ◽  
Fine Specificity ◽  
Specific Memory ◽  
Cancer Testis

Abstract Abstract 5087 Background: Cancer-testis antigens (CTA) are attractive targets for cancer immunotherapy based on their tumor-restricted expression and immunogenicity. A number of CTA, including Melanoma-associated antigen 3 (MAGE-A3), are already under clinical investigation and CTA have been shown to induce strong T cell and humoral immunity in cancer patients receiving active immunotherapy. However, little is known about the fine specificity and the function of vaccine-induced humoral immune responses and it is unclear how they relate to spontaneous CTA-specific immune responses occurring in a minority of patients. Methods: We have performed a longitudinal analysis of spontaneously occurring antibody responses against the CT antigen MAGE-A3 in sera (N=1537), which were collected from patients with multiple myeloma (N=355) over a period of 6 years. Antibody titers were determined by ELISA technique and a B cell ELISPOT assay was applied to estimate the number of MAGEA3-specific memory B cells in peripheral blood of the patients. Fine specificity of the antibody responses was examined using overlapping 20mer peptides spanning the whole sequence of MAGE-A3. The given IgG subtype was determined, and the quality of MAGE-A3-specific antibodies was analyzed using western blot as well as affinity assays. Results were compared to those obtained with MAGE-A3-specific antibody responses induced by vaccination with full-length MAGE-A3 protein and adjuvants AS02B or AS15 in patients with non-small cell lung cancer (NSCLC; N=15). Results: Out of 355 myeloma patients 4 (1.1%) evidenced spontaneous antibody responses against MAGE-A3 at least at one point during the course of their disease. Spontaneously occurring anti-MAGE-A3 humoral responses were usually of low titer. In contrast, all of the vaccinated patients showed high-titered and persisting antibody responses which usually appeared around week 6 after the first application of the vaccine. Accordingly, we found high frequencies of vaccine-induced MAGE-A3-specific memory B cells in the peripheral blood of NSCLC patients while they remained undetectable in most myeloma patients. Vaccine-induced antibody responses underwent affinity maturation reaching affinity levels of spontaneous immune responses after repeated cycles of treatment. MAGE-A3-specific antibodies consisted of IgG1 and IgG3>IgG2>IgG4 subtypes in vaccinated patients whereas spontaneously occurring antibodies were mainly of the IgG2 subtype. Spontaneous as well as vaccine-induced IgG antibodies both recognized the natural full-length protein. Analysis of the fine specificity of the antibody responses revealed that vaccine-induced antibodies recognized a much larger number of MAGE-A3 epitopes than spontaneously occurring antibodies. However, both, spontaneous as well as vaccine-induced responses, most frequently and strongly recognized a specific region within the MAGE-A3 protein corresponding to amino acids 51–70. Conclusions This study demonstrates for the first time important qualitative differences between spontaneously occurring and vaccine-induced antibody responses against the MAGE-A3 antigen in cancer patients. While the potential of both types of antibody responses to promote antigen uptake and induction of T cell responses by antigen-presenting cells might differ, they both recognized the same restricted region within the MAGE-A3 protein. The latter finding might be of importance for the design of future immunotherapies targeting MAGE-A3. Disclosures: No relevant conflicts of interest to declare.

Advance directives: Cancer patients’ preferences and family-based decision making.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 18-18
Author(s):  
Xing Li ◽  
Zhi-Huan Lin ◽  
Ying-Fen Hong ◽  
Xiao-kun Ma ◽  
Dong-hao Wu ◽  
...  
Keyword(s):  
Decision Making ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Advance Directives ◽  
Correlational Analysis ◽  
Invasive Treatment ◽  
Medical Decisions ◽  
Anti Cancer ◽  
Family Based ◽  
Chinese Cancer Patients

18 Background: Advance directives (ADs) are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, which might violate patients’ personal will. This study was aimed to examine the acceptance of ADs among Chinese cancer patients and their families and patient participation in this procedure. Finally, to analyze the moral risk involved. Methods: Participants included 412 adult cancer patients from 9 leading hospitals across China. An AD was introduced to the main decision makers for each patient; if they wished to sign it, the AD would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients’ awareness of their disease, and participation in an AD. Results: A total of 246 patients and their family members rejected systematic discussion of AD, the majority (95.5%) of whom were under anti-cancer treatment. An additional 166 patients or their families accepted the concept of an AD and signed an AD to give up invasive treatment. This decision was make shortly after termination of anti-cancer therapy. Correlational analysis revealed that patients living in villages and who were subordinate members in their families tended to accept an AD. Of these, only 24 patients participated in the decision making. Correlational analysis revealed that patients with a better financial situation, living in cities, and superordinate status in their families tended to participate in the AD discussion, as well as those who usually made medical decisions themselves. Nearly all the patients deciding their own AD knew their entire situation, including diagnosis and prognosis. For 101 patients, anti-cancer therapy was ended prematurely, with as many as 37 patients not told about their potential loss of health interests. Conclusions: ADs were widely accepted among Chinese cancer patients when anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an AD. Thus, AD could be formally introduced to the family of Chinese cancer patients after termination of anti-cancer therapy.

Monitoring oral anti-cancer therapy adherence in cancer patients using web based application guided communication compared with nurse counseling in a community cancer center.

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 88-88
Author(s):  
Milana V. Dolezal ◽  
Vivian Leong ◽  
Rajesh Behl
Keyword(s):  
Cancer Therapy ◽  
Cancer Patients ◽  
Effective Communication ◽  
Smart Device ◽  
Cancer Center ◽  
Free Text ◽  
Communication Tools ◽  
Web Based ◽  
Electronic Alerts ◽  
Anti Cancer

88 Background: Smart phone web based applications (apps) can be effective communication tools for monitoring compliance and increasing adherence to oral anti-cancer therapy in the outpatient setting. Methods: Cancer patients age 18-90 treated with various oral anti-cancer therapies were recruited to this prospective, 3 month observational trial at our large community cancer center to determine feasibility of using an app for oral anti-cancer therapy compliance. Enrolled patients are randomized to either Arm 1 App arm and nurse counseling or Arm 2 nurse counseling only. The free apps MyMeds and Medisafe incorporate medication reminders and record doses. Patients complete the validated RAND 36- item quality of life (QOL) questionnaire and a free text feedback. Results: 91 patients were screened between 11/2015 to 9/2016 (45 declined enrollment due to various factors). 46 patients were randomized with 25 to Arm 1 and 21 to Arm 2. Demographics included 10 men (various tumor types but mostly multiple myeloma) and 36 women; 22 with breast cancer. MyMeds app lacked the necessary real-time communication so patients were switched to the MediSafe app which features email alerts. 15 patients have completed the study through Month 3. Four patients on Arm 1 missing their monthly visit or were non-compliant with the app. 23 patients remain active in the study. Differences are a higher QOL score in Arm 1 vs Arm 2 in measured domains of Energy/Fatigue (56% in Arm 1 compared to 44% for Arm 2) and Pain (72% in Arm 1 compared to 58% in Arm 2). Patients randomized to the app found the electronic alerts very helpful. Conclusions: Our limited pilot study demonstrated the potential of smart device apps as effective communication tools for improving patients’ adherence to oral anti-cancer therapy and QOL. Ultimately, convenient ways to monitor patients’ compliance with anti-cancer therapy will impact survival and facilitate provider-patient communication.

scholarly journals Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 159
Author(s):  
Achmad Kemal Harzif ◽  
Budi Wiweko ◽  
Putri Addina ◽  
Kartika Iswaranti ◽  
Melisa Silvia ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Patients ◽  
Reproductive Function ◽  
Cross Sectional Study ◽  
Reproductive Age ◽  
Cancer Treatments ◽  
Cross Sectional ◽  
Cancer Group ◽  
Anti Cancer ◽  
Female Cancer Patients

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched). The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.

scholarly journals Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 159
Author(s):  
Achmad Kemal Harzif ◽  
Budi Wiweko ◽  
Putri Addina ◽  
Kartika Iswaranti ◽  
Melisa Silvia ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Patients ◽  
Reproductive Function ◽  
Cross Sectional Study ◽  
Reproductive Age ◽  
Cancer Treatments ◽  
Cross Sectional ◽  
Cancer Group ◽  
Anti Cancer ◽  
Female Cancer Patients

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched). The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.

scholarly journals Anti-cancer Therapy Leads to Increased Cardiovascular Susceptibility to COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Caroline Lozahic ◽  
Helen Maddock ◽  
Hardip Sandhu
Keyword(s):  
Cancer Therapy ◽  
Cancer Patients ◽  
Respiratory Disease ◽  
Myocardial Injury ◽  
Cardiac Injury ◽  
Cardiovascular Complications ◽  
World Health ◽  
Cancer Drug ◽  
Health Crisis ◽  
Anti Cancer

Anti-cancer treatment regimens can lead to both acute- and long-term myocardial injury due to off-target effects. Besides, cancer patients and survivors are severely immunocompromised due to the harsh effect of anti-cancer therapy targeting the bone marrow cells. Cancer patients and survivors can therefore be potentially extremely clinically vulnerable and at risk from infectious diseases. The recent global outbreak of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its infection called coronavirus disease 2019 (COVID-19) has rapidly become a worldwide health emergency, and on March 11, 2020, COVID-19 was declared a global pandemic by the World Health Organization (WHO). A high fatality rate has been reported in COVID-19 patients suffering from underlying cardiovascular diseases. This highlights the critical and crucial aspect of monitoring cancer patients and survivors for potential cardiovascular complications during this unprecedented health crisis involving the progressive worldwide spread of COVID-19. COVID-19 is primarily a respiratory disease; however, COVID-19 has shown cardiac injury symptoms similar to the cardiotoxicity associated with anti-cancer therapy, including arrhythmia, myocardial injury and infarction, and heart failure. Due to the significant prevalence of micro- and macro-emboli and damaged vessels, clinicians worldwide have begun to consider whether COVID-19 may in fact be as much a vascular disease as a respiratory disease. However, the underlying mechanisms and pathways facilitating the COVID-19-induced cardiac injury in cancer and non-cancer patients remain unclear. Investigations into whether COVID-19 cardiac injury and anti-cancer drug-induced cardiac injury in cancer patients and survivors might synergistically increase the cardiovascular complications and comorbidity risk through a “two-hit” model are needed. Identification of cardiac injury mechanisms and pathways associated with COVID-19 development overlapping with anti-cancer therapy could help clinicians to allow a more optimized prognosis and treatment of cancer survivors suffering from COVID-19. The following review will focus on summarizing the harmful cardiovascular risk of COVID-19 in cancer patients and survivors treated with an anti-cancer drug. This review will improve the knowledge of COVID-19 impact in the field of cardio-oncology and potentially improve the outcome of patients.

scholarly journals Systems biological assessment of human immunity to BNT162b2 mRNA vaccination

2021 ◽  
Author(s):  
Bali Pulendran ◽  
Prabhu S Arunachalam
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Booster Vaccination ◽  
Fold Increase ◽  
Biological Assessment ◽  
Interferon Response ◽  
Innate Response ◽  
Booster Immunization ◽  
Inflammatory Monocytes

Abstract The emergency use authorization of two COVID-19 mRNA vaccines in less than a year since the emergence of SARS-CoV-2, represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems biological approach to comprehensively profile the innate and adaptive immune responses in 56 healthy volunteers vaccinated with the Pfizer-BioNTech mRNA vaccine. Vaccination resulted in robust production of neutralizing antibodies (nAbs) against the parent strain and the variant of concern, B.1.351, but no induction of autoantibodies, and significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. The innate response induced within the first 2 days of booster vaccination was profoundly increased, relative to the response at corresponding times after priming. Thus, there was a striking increase in the: (i) frequency of CD14+CD16+ inflammatory monocytes; (ii) concentration of IFN-y in the plasma, which correlated with enhanced pSTAT3 and pSTAT1 levels in monocytes and T cells; and (iii) transcriptional signatures of innate responses characteristic of antiviral vaccine responses against pandemic influenza, HIV and Ebola, within 2 days following booster vaccination compared to primary vaccination. Consistent with these observations, single-cell transcriptomics analysis of 242,479 leukocytes demonstrated a ~100-fold increase in the frequency of a myeloid cluster, enriched in a signature of interferon-response transcription factors (TFs) and reduced in AP-1 TFs, one day after secondary immunization, at day 21. Finally, we delineated distinct molecular pathways of innate activation that correlate with CD8 T cell and nAb responses and identified an early monocyte-related signature that was associated with the breadth of the nAb response against the B1.351 variant strain. Collectively, these data provide insights into the immune responses induced by mRNA vaccines and demonstrate their capacity to stimulate an enhanced innate response following booster immunization.

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