Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

Spiliopoulou, Pavlina; Rensburg, Helena J. Janse van; Avery, Lisa; Kulasingam, Vathany; Razak, Albiruni Ryan Abdul; Bédard, Philippe L.; Hansen, Aaron Richard; Chruscinski, Andrzej; Wang, Ben; Kulikova, Maria; Chen, Rachel; Speers, Vanessa; Nguyen, Alisa; Lee, Jasmine; Coburn, Bryan; Spreafico, Anna; Siu, Lillian L.

doi:10.1038/s41419-022-05548-4

Cited by 6 publications

(5 citation statements)

References 54 publications

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“…A total of 162 antigens, customized based on tissues or organs most frequently affected by irAEs were selected (a list of the antigens used for this study is provided in Supplementary Table 1 ). The antigens included in the panel are associated with multiple autoimmune disorders and have been used to screen for autoantibodies in a variety of conditions such as heart failure/heart transplantation [ 44 , 50 ], kidney transplantation [ 51 ], liver transplantation [ 52 ], lung transplantation [ 53 ], systemic autoimmune rheumatic diseases [ 54 ], and post-covid vaccination [ 55 ]. Antigens were diluted in PBS to 0.2 mg/ml and subsequently stored at -80 °C.…”

Section: Methodsmentioning

confidence: 99%

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Genta,

Lajkosz,

Yee

et al. 2023

J Exp Clin Cancer Res

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Background Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb). Methods We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity. Results A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009). Conclusions Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).

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Section: Methodsmentioning

confidence: 99%

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Genta,

Lajkosz,

Yee

et al. 2023

J Exp Clin Cancer Res

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“…Impaired PD-1/PD-L1 function plays an important role in many autoimmune diseases [149]. The fact that the activation of PD-1 is essential for the prevention of autoimmunity caused by the mRNA vaccines is shown in a study involving cancer(+) patients [150]. These patients were under immunotherapy treatment with checkpoint signalling inhibitors that block PD-L1 expression and therefore PD-1 activation [41].…”

Section: Pd-l1 Upregulation Following Mrna Vaccinationmentioning

confidence: 99%

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

Kyriakopoulos,

Nigh,

McCullough

et al. 2024

Preprint

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When an antigen stimulates the immune system, specific T regulatory (Treg) and T effector (Teff) subpopulations develop from naïve T cells. The Treg cell population will produce the memory Treg (mTreg) cells against that specific antigen. An inappropriate homeostatic balance among Teff, Treg and mTreg cells can direct the immune system toward either cancer or autoimmunity. When cancer is present, Treg cells suppress anti-tumor immunity, and, when cancer is absent, Treg cells play the beneficial role of preventing the development of autoimmunity. In this review, we analyze Treg responses after SARS-CoV-2 mRNA vaccination and find distinct pathological responses under differing conditions. In cancer patients, the degree of disease progression depends on the cancer status at the time of vaccination and the type of cancer treatment they receive concurrently. We hypothesize that migration of circulating dendritic cells and mTreg cells back to the thymus accelerates thymic involution, a direct cause of immunosenescence. In summary, the Treg responses produced after mRNA vaccination and the subsequent mRNA-encoded SARS-CoV-2 spike protein expression may lead to a harmful influence on the immune system of vaccinees, and subsequent accelerated development of cancer and autoimmune disease. These mechanisms are consistent with both epidemiological findings and case reports.

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“…14,15 Elevations of antibodies following SARS-CoV-2 infection or vaccination may include a concomitant rise in autoantibodies associated with adverse events in COVID-19 patients. 16,17 In parallel to patients treated with CCP, passive transfer of donor SARS-CoV-2 antibodies is recognized to occur in transfusion recipients without COVID-19, including recipients of platelet products. 18 Transfusion of SARS-CoV-2 antibodies or autoantibodies in high plasma volume blood components may impact outcomes in recipients without COVID-19, and the receipt of blood from previously infected or vaccinated blood donors has been a concern raised by some patient advocacy groups and even lawmakers.…”

Section: Introductionmentioning

confidence: 99%

“…Neutralizing and anti‐spike antibodies in blood donors are known to increase by several logs following subsequent exposure to novel SARS‐CoV‐2 variants or vaccine boosting 14,15 . Elevations of antibodies following SARS‐CoV‐2 infection or vaccination may include a concomitant rise in autoantibodies associated with adverse events in COVID‐19 patients 16,17 . In parallel to patients treated with CCP, passive transfer of donor SARS‐CoV‐2 antibodies is recognized to occur in transfusion recipients without COVID‐19, including recipients of platelet products 18 .…”

Section: Introductionmentioning

confidence: 99%

Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS‐CoV‐2 infection and vaccination

Roubinian,

Greene,

Liu

et al. 2023

Transfusion

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BackgroundThe safety of transfusion of SARS‐CoV‐2 antibodies in high plasma volume blood components to recipients without COVID‐19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS‐CoV‐2 infection and vaccination was associated with changes in outcomes in hospitalized patients without COVID‐19.MethodsWe conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre‐COVID‐19 (3/1/2018–2/29/2020), COVID‐19 pre‐vaccine (3/1/2020–2/28/2021), and COVID‐19 post‐vaccine (3/1/2021–8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAmong 21,750 hospitalizations of 18,584 transfusion recipients without COVID‐19, there were 697 post‐transfusion thrombotic events, and oxygen requirements were increased in 1751 hospitalizations. Intensive care unit length of stay (n = 11,683) was 3 days (interquartile range 1–5), hospital mortality occurred in 3223 (14.8%), and 30‐day rehospitalization in 4144 (23.7%). Comparing the pre‐COVID, pre‐vaccine and post‐vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p = .22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p = .41). In parallel, there were no trends across study periods for ICU length of stay (p = .83), adjusted hospital mortality (OR 1.0 [95% CI 0.9–1.0]; p = .36), or 30‐day rehospitalization (p = .29).DiscussionTransfusion of plasma and platelet blood components collected during the pre‐vaccine and post‐vaccine periods of the COVID‐19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID‐19.

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Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

Cited by 6 publications

References 54 publications

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS‐CoV‐2 infection and vaccination

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