IMP321 (sLAG-3) safety and T cell response potentiation using an influenza vaccine as a model antigen: A single-blind phase I study

Vaccine ◽  
2007 ◽  
Vol 25 (24) ◽  
pp. 4641-4650 ◽  
Author(s):  
Chrystelle Brignone ◽  
Caroline Grygar ◽  
Manon Marcu ◽  
Gaëlle Perrin ◽  
Frédéric Triebel
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Phase I ◽  
Cell Response ◽  
Phase I Study ◽  
T Cell Response ◽  
Antigen A ◽  
Single Blind

Impaired Specific B-Cell While Preserved T-Cell Response Against Influenza Vaccine in SOT Recipients.

2014 ◽  
Vol 98 ◽  
pp. 188
Author(s):  
D. Zbinden ◽  
M. Pascual ◽  
S. Lartey ◽  
R. Pathirana ◽  
G. Bredholt ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
B Cell ◽  
Cell Response ◽  
T Cell Response

scholarly journals Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001157
Author(s):  
Juliane Schuhmacher ◽  
Sonja Heidu ◽  
Torben Balchen ◽  
Jennifer Rebecca Richardson ◽  
Camilla Schmeltz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Phase I ◽  
Cell Response ◽  
Small Gtpase ◽  
T Cell Response ◽  
Effector Memory ◽  
Tolerability Profile

BackgroundPeptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells.MethodsTwenty-two patients who had previously undergone radical prostatectomy received subcutaneous injections of 0.1 mg of a single RhoC-derived 20mer peptide emulsified in Montanide ISA-51 every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. The drug safety and vaccine-specific immune responses were assessed during treatment and thereafter within a 13-month follow-up period. Serum level of prostate-specific antigen was measured up to 26 months postvaccination.ResultsMost patients (18 of 21 evaluable) developed a strong CD4 T cell response against the vaccine, which lasted at least 10 months following the last vaccination. Three promiscuouslypresented HLA-class II epitopes were identified. Vaccine-specific CD4 T cells were polyfunctional and effector memory T cells that stably expressed PD-1 (CD279) and OX-40 (CD134), but not LAG-3 (CD223). One CD8 T cell response was detected in addition. The vaccine was well tolerated and no treatment-related adverse events of grade ≥3 were observed.ConclusionTargeting of RhoC induced a potent and long-lasting T cell immunity in the majority of the patients. The study demonstrates an excellent safety and tolerability profile. Vaccination against RhoC could potentially delay or prevent tumor recurrence and metastasis formation.Trial registration numberNCT03199872.

scholarly journals The T cell receptor repertoire reflects the dynamics of the immune response to vaccination

2021 ◽  
Author(s):  
Kevin Mohammed ◽  
Austin Meadows ◽  
Sandra Hatem ◽  
Viviana Simon ◽  
Anitha D Jayaprakash ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Influenza Vaccine ◽  
T Cell Receptor ◽  
Cell Response ◽  
Cell Receptor ◽  
Physical Symptoms ◽  
T Cell Response ◽  
Tcr Repertoire

Early, high-resolution metrics are needed to ascertain the immune response to vaccinations. The T cell receptor (TCR), a heterodimer of one α and one β chain, is a promising target, with the complete TCR repertoire reflecting the T cells present in an individual. To this end, we developed Tseek, an unbiased and accurate method for profiling the TCR repertoire by sequencing the TCR α and β chains and developing a suite of tools for repertoire analysis. An added advantage is the ability to non-invasively analyze T cells in peripheral blood mononuclear cells (PBMCs). Tseek and the analytical suite were used to explore the T cell response to both the COVID-19 mRNA vaccine (n=9) and the seasonal inactivated Influenza vaccine (n=5) at several time points. Neutralizing antibody titers were also measured in the covid vaccine samples. The COVID-19 vaccine elicited a broad T cell response involving multiple expanded clones, whereas the Influenza vaccine elicited a narrower response involving fewer clones. Many distinct T cell clones responded at each time point, over a month, providing temporal details lacking in the antibody measurements, especially before the antibodies are detectable. In individuals recovered from a SARS-CoV-2 infection, the first vaccine dose elicited a robust T cell response, while the second dose elicited a comparatively weaker response, indicating a saturation of the response. The physical symptoms experienced by the recipients immediately following the vaccinations were not indicative of the TCR/antibody responses, while a weak TCR response seemed to presage a weak antibody response. We also found that the TCR repertoire acts as an individual fingerprint: donors of blood samples taken years apart could be identified solely based upon their TCR repertoire, hinting at other surprising uses the TCR repertoire may have. These results demonstrate the promise of TCR repertoire sequencing as an early and sensitive measure of the adaptive immune response to vaccination, which can help improve immunogen selection and optimize vaccine dosage and spacing between doses.

scholarly journals Suppression by Thimerosal of Ex-Vivo CD4+ T Cell Response to Influenza Vaccine and Induction of Apoptosis in Primary Memory T Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e92705 ◽  
Author(s):  
Emily Loison ◽  
Béatrice Poirier-Beaudouin ◽  
Valérie Seffer ◽  
Audrey Paoletti ◽  
Vered Abitbol ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Influenza Vaccine ◽  
Cell Response ◽  
Memory T Cells ◽  
Ex Vivo ◽  
T Cell Response ◽  
Primary Memory ◽  
Cd4 T Cell ◽  
Induction Of Apoptosis

315 W0180 novel anti-VISTA antibody: Rationale for target patient population and first-in-human trial design in monotherapy and in combination with anti-PD1 antibody

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A341-A341
Author(s):  
Ignacio Melero ◽  
Carlos Gomez-Roca ◽  
Pierre Ferre ◽  
Pierre Ferre ◽  
Eric Chetaille ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phase I ◽  
Dose Escalation ◽  
Immune Checkpoint ◽  
Cell Response ◽  
T Cell Response ◽  
Pharmacokinetic Data ◽  
List Type ◽  
Ethic Committee

BackgroundV-domain Ig suppressor of T cell Activation (VISTA) is a negative checkpoint regulator of T cell response.1 VISTA is expressed within the tumor microenvironment, where its blockade can enhance antitumor immune responses.2 Furthermore, an increase in VISTA expression has been reported after treatment by anti-PD1/L1 and anti-CTLA4.3,4 This confirms that VISTA may play a key role as a mechanism of resistance to the currently used immunotherapies. VISTA/PSGL1 pH-selective biochemical interaction has been recently demonstrated.5 VISTA and PSGL1 expression pattern, their correlation and their relationship to myeloid infiltrates have been evaluated in samples from patients with solid tumors. K01401-020 (W0180) is a novel anti-VISTA antibody that has the potential to activate T cells when given as a monotherapy6, and thus to generate added activity when combined with anti-PD1/L1 antibodies in cancer patients.MethodsThis phase I/Ib for W0180 consists of 2 parts: an initial dose escalation phase I followed by an expansion cohorts phase Ib. In the dose escalation phase, 2 cohorts of patients will be assessed in parallel: the first cohort will be given W0180 as a single agent and the second cohort will receive W0180 in combination with pembrolizumab. The first dose and the schedule of administration of W0180 in combination with pembrolizumab will be determined using safety and pharmacokinetic data generated in monotherapy. The phase I will allow to determine the Maximum Tolerated Dose and Schedule (MTDS), to characterize Dose-Limiting Toxicities (DLTs) and explore pharmacodynamic activity of W0180 in monotherapy and combination with pembrolizumab. The dose-toxicity relationships will support the dose escalation process and will be used to assess the MTDS and recommended doses for expansion. Following completion of the dose escalation phase, the expansion phase will enroll cohorts of patients with homogeneous tumors to validate the dose/schedule, assess preliminary activity and to explore the potential relationship with VISTA and PSGL1 expression.ResultsN/AConclusionsN/ATrial RegistrationN/AEthics ApprovalThe study was approved by National French Ethic committee (CPP Ile de France V) and National Spanish Ethic committee (Comité Ético de Investigación Clínica de Navarra) and was registered in the European database (EudraCT: 2019-002299-15).ConsentN/AReferencesWang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, Lu LF, Gondek D, Wang Y, Fava RA, Fiser A, Almo S, Noelle RJ, VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med 2011;208:577–92.Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O’Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle R, VISTA is an immune checkpoint molecule for human T cells. Cancer Res 2014;74:1924–32.Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, Zhao H, Chen J, Chen H, Efstathiou E, Troncoso P, Allison JP, Logothetis CJ, Wistuba II, Sepulveda MA, Sun J, Wargo J, Blando J, Sharma P, VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med 2017;23:551–555.Kakavand H, Jackett LA, Menzies AM, Gide TN, Carlino MS, Saw RPM, Thompson JF, Wilmott JS, Long GV, Scolyer RA, Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients. Mod Pathol 2017;30:1666–1676.Johnston RJ, Su LJ, Pinckney J, Critton D, Boyer E, Krishnakumar A, Corbett M, Rankin AL, Dibella R, Campbell L, Martin GH, Lemar H, Cayton T, Huang RY, Deng X, Nayeem A, Chen H, Ergel B, Rizzo JM, Yamniuk AP, Dutta S, Ngo J, Shorts AO, Ramakrishnan R, Kozhich A, Holloway J, Fang H, Wang YK, Yang Z, Thiam K, Rakestraw G, Rajpal A, Sheppard P, Quigley M, Bahjat KS, Korman AJ, VISTA is an acidic pH-selective ligand for PSGL-1. Nature 2019;574:565–570Libon C, Vandenberghe I, Marlin R, Gros W, Leonec M, Gomez-Pacheco M, Gallouet M, Fraboul F, Mahfoudi A, Dereuddre-Bosquet N, Ferré P, K0401-020 anti-VISTA antibody monotherapy increases specific CD8 T cell response in non-human primates. AACR Annual meeting 2020.

scholarly journals A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

2016 ◽  
Vol 168 ◽  
pp. 72-87 ◽  
Author(s):  
Stéphane Pillet ◽  
Éric Aubin ◽  
Sonia Trépanier ◽  
Diane Bussière ◽  
Michèle Dargis ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Cell Response ◽  
T Cell Response ◽  
Healthy Adults ◽  
Virus Like Particle ◽  
Reactive Antibody

scholarly journals Superior antigen-specific CD4+T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Robert B Couch ◽  
José M Bayas ◽  
Covadonga Caso ◽  
Innocent Nnadi Mbawuike ◽  
Concepción Núñez López ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Cell Response ◽  
Randomised Trial ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Trivalent Influenza Vaccine

Personalized viral-based prime/boost immunotherapy targeting patient-specific or shared neoantigens: Immunogenicity, safety, and efficacy results from two ongoing phase I studies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3137-3137
Author(s):  
Charles G. Drake ◽  
Melissa Lynne Johnson ◽  
Alexander I. Spira ◽  
Gulam Abbas Manji ◽  
David Paul Carbone ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Phase I ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Patient Specific ◽  
Clinical Activity ◽  
Skin Reactions ◽  
Phase I Studies

3137 Background: Neoantigens are key targets of a tumor-specific immune response and CD8 T cells targeting neoantigens drive clinical benefit in patients (pts) treated with checkpoint inhibitors. Methods: Two Phase I studies are being conducted to assess the safety, immunogenicity, and early clinical activity of a viral-based neoantigen-targeting prime/boost immunotherapy aimed at maximizing the CD8 T cell response. Both studies use a chimpanzee adenovirus prime followed by increasing doses of repeat boosts with a self-amplifying mRNA in combination with IV nivolumab +/- SC ipilimumab. In the first study, GO-004, patient-specific neoantigens are predicted using Gritstone's EDGE model and incorporated into both prime/boost vectors. In GO-005, shared neoantigens derived from common driver mutations (including several from KRAS) are encoded in off-the-shelf prime/boost vectors. Results: To date, 12 pts have been treated: 6 pts with GEA, NSCLC, or MSS-CRC (GO-004) and 6 pts with NSCLC, MSS-CRC, or PDA (GO-005) with all pts receiving IV nivolumab and 5 pts also receiving SC ipilimumab. Nine pts continue to receive study treatment. No DLTs have been observed. Treatment-related AEs are reversible and include Grade 1/2 fever (7/12), injection site reactions (4/12), fatigue (3/12), diarrhea (2/12), hypotension (2/12), pruritus (2/12), skin reactions (2/12), anorexia (1/12), dyspnea (1/12), hyponatremia (1/12), infusion-related reactions (1/12), myalgia (1/12), and asymptomatic Grade 3 CK elevation (1/12). At the time of analysis, 8 of 12 pts with ≥ 1 radiographic assessment have a best response of stable disease (SD) (3) and progressive disease (PD) (4), and one pt with no evaluable disease at baseline continues on study > 8 months. In GO-005, 1 pt with SD has a 20% reduction in tumor dimensions that correlates with a decrease in ctDNA. In 4 pts in GO-004 analyzed to date, all pts showed substantial neoantigen-specific CD8 T cell responses to multiple neoantigens after priming which increase further in 2 of 3 pts analyzed after subsequent boosts. In GO-005, 1 of 3 pts showed a robust KRAS G12C-specific CD8 T cell response. Induced T cells express IFNg and granzyme B, consistent with an effector response. Conclusions: Taken together, these early data support the tolerability of a viral-based prime/boost immunotherapy, demonstrate marked immunogenicity, and are consistent with potential clinical activity. Additional pts and data at higher dose levels will be presented. Clinical trial information: NCT03639714, NCT03953235 .

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