The Importance of Cellular Immunity in the Development of Vaccines and Therapeutics for COVID-19

Schlom, Jeffrey; Donahue, Renee N.

doi:10.1093/infdis/jiaa415

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…1 B on samples more than 50 days post-PCR, the percentage of positive results tends to decrease as recently described for neutralizing antibodies [ 8 , 9 ]. All these results raise the question of the role of humoral immunity in relation to cellular immunity in combating this infection and its persistence [ 10 , 11 ]. Although we cannot compare the periods in this Fig.…”

Section: Discussionmentioning

confidence: 99%

Comparison of different serological assays for SARS-CoV-2 in real life

Brochot

Demey

Handala

et al. 2020

Journal of Clinical Virology

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Background The emergence of the global SARS-CoV-2 pandemic required the rapid and large-scale deployment of PCR and serological tests in different formats. Objectives Real-life evaluation of these tests is needed. Using 168 samples from patients hospitalized for COVID-19, non-hospitalized patients but infected with SARS-CoV-2, patients participating in screening campaigns, and samples from patients with a history of other seasonal coronavirus infections, we evaluated the clinical performance of 5 serological assays widely used worldwide (WANTAI®, BIORAD®, EUROIMMUN®, ABBOTT® and LIAISON®). Results For hospitalized patients, all these assays showed a sensitivity of 100 % from day 9 after the symptoms onset. On the other hand, sensitivity was much lower for patients who did not require hospitalization for COVID-19 confirmed by PCR (from 91.6 % for WANTAI® to 69 % for LIAISON®). These differences do not seem to be due to the antigens chosen by the manufacturers but more to the test formats (IgG detection versus total antibodies). In addition, more than 50 days after a positive PCR for CoV-2-SARS the proportion of positive patients seem to decrease. We did not observe any significant cross-reactions for these techniques with the four other seasonal coronaviruses. Conclusion In conclusion, the evaluation and knowledge of the serological tests used is important and should require an optimized strategy adaptation of the analysis laboratories to best meet patient’s expectations in the face of this health crisis.

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Section: Discussionmentioning

confidence: 99%

Comparison of different serological assays for SARS-CoV-2 in real life

Brochot

Demey

Handala

et al. 2020

Journal of Clinical Virology

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“…In the dose-escalation part, cryopreserved peripheral blood mononuclear cells (PBMCs) were examined by multicolor flow cytometry to identify 135 peripheral immune cell subsets 15 using the methodology described previously. 16 17 Additionally, in the dose-escalation part, gene expression analyses were performed on total RNA extracted from cryopreserved PBMCs that had been collected from patients before and after 15 days of treatment using the Qiagen RNeasy Plus Minikit (Valencia, California, USA) per the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

First-in-human phase Ib trial of M9241 (NHS-IL12) plus avelumab in patients with advanced solid tumors, including dose expansion in patients with advanced urothelial carcinoma

Strauss

Deville

Sznol

et al. 2023

J Immunother Cancer

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BackgroundIn preclinical studies, combining M9241 (a novel immunocytokine containing interleukin (IL)-12 heterodimers) with avelumab (anti-programmed death ligand 1 antibody) resulted in additive or synergistic antitumor effects. We report dose-escalation and dose-expansion results from the phase Ib JAVELIN IL-12 trial investigating M9241 plus avelumab.MethodsIn the dose-escalation part of JAVELIN IL-12 (NCT02994953), eligible patients had locally advanced or metastatic solid tumors; in the dose-expansion part, eligible patients had locally advanced or metastatic urothelial carcinoma (UC) that had progressed with first-line therapy. Patients received M9241 at 4, 8, 12, or 16.8 µg/kg every 4 weeks (Q4W) plus avelumab 10 mg/kg every 2 weeks (Q2W, dose levels (DLs) 1–4) or M9241 16.8 µg/kg Q4W plus avelumab 800 mg once a week for 12 weeks followed by Q2W (DL5/dose expansion). Primary endpoints for the dose-escalation part were adverse events (AEs) and dose-limiting toxicities (DLTs), and those for the dose-expansion part were confirmed best overall response (BOR) per investigator (Response Evaluation Criteria in Solid Tumors V.1.1) and safety. The dose-expansion part followed a two-stage design; 16 patients were enrolled and treated in stage 1 (single-arm part). A futility analysis based on BOR was planned to determine whether stage 2 (randomized controlled part) would be initiated.ResultsAt data cut-off, 36 patients had received M9241 plus avelumab in the dose-escalation part. All DLs were well tolerated; one DLT occurred at DL3 (grade 3 autoimmune hepatitis). The maximum-tolerated dose was not reached, and DL5 was declared the recommended phase II dose, considering an observed drug–drug interaction at DL4. Two patients with advanced bladder cancer (DL2 and DL4) had prolonged complete responses. In the dose-expansion part, no objective responses were recorded in the 16 patients with advanced UC; the study failed to meet the criterion (≥3 confirmed objective responses) to initiate stage 2. Any-grade treatment-related AEs occurred in 15 patients (93.8%), including grade ≥3 in 8 (50.0%); no treatment-related deaths occurred. Exposures for avelumab and M9241 concentrations were within expected ranges.ConclusionsM9241 plus avelumab was well tolerated at all DLs, including the dose-expansion part, with no new safety signals. However, the dose-expansion part did not meet the predefined efficacy criterion to proceed to stage 2.

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