A Potent Cancer Vaccine Adjuvant System for Particleization of Short, Synthetic CD8+ T Cell Epitopes

ACS Nano ◽  
2021 ◽  
Author(s):  
Xuedan He ◽  
Shiqi Zhou ◽  
Wei-Chiao Huang ◽  
Amal Seffouh ◽  
Moustafa T. Mabrouk ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Vaccine ◽  
Cd8 T Cell ◽  
Vaccine Adjuvant ◽  
T Cell Epitopes ◽  
Adjuvant System

scholarly journals High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4+ and CD8+ T-Cell Epitopes

2018 ◽  
Vol 8 ◽  
Author(s):  
Fanny Onodi ◽  
Chahrazed Maherzi-Mechalikh ◽  
Alice Mougel ◽  
Nadine Ben Hamouda ◽  
Charlotte Taboas ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Vaccine ◽  
Therapeutic Efficacy ◽  
Cd8 T Cell ◽  
T Cell Epitopes

HLA-B*27 subtype specificity determines the targeting of HLA-B*27 restricted HCV-specific CD8+ T cell epitopes

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
K Nitschke ◽  
J Schmidt ◽  
HE Blum ◽  
R Thimme ◽  
C Neumann-Haefelin
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Subtype Specificity

scholarly journals Identification of Promiscuous African Swine Fever Virus T-Cell Determinants Using a Multiple Technical Approach

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 29
Author(s):  
Laia Bosch-Camós ◽  
Elisabet López ◽  
María Jesús Navas ◽  
Sonia Pina-Pedrero ◽  
Francesc Accensi ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Cd8 T Cell ◽  
Protective Role ◽  
Full Length ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear

The development of subunit vaccines against African swine fever (ASF) is mainly hindered by the lack of knowledge regarding the specific ASF virus (ASFV) antigens involved in protection. As a good example, the identity of ASFV-specific CD8+ T-cell determinants remains largely unknown, despite their protective role being established a long time ago. Aiming to identify them, we implemented the IFNγ ELISpot as readout assay, using as effector cells peripheral blood mononuclear cells (PBMCs) from pigs surviving experimental challenge with Georgia2007/1. As stimuli for the ELISpot, ASFV-specific peptides or full-length proteins identified by three complementary strategies were used. In silico prediction of specific CD8+ T-cell epitopes allowed identifying a 19-mer peptide from MGF100-1L, as frequently recognized by surviving pigs. Complementarily, the repertoire of SLA I-bound peptides identified in ASFV-infected porcine alveolar macrophages (PAMs), allowed the characterization of five additional SLA I-restricted ASFV-specific epitopes. Finally, in vitro stimulation studies using fibroblasts transfected with plasmids encoding full-length ASFV proteins, led to the identification of MGF505-7R, A238L and MGF100-1L as promiscuously recognized antigens. Interestingly, each one of these proteins contain individual peptides recognized by surviving pigs. Identification of the same ASFV determinants by means of such different approaches reinforce the results presented here.

418 A phase 1, dose escalation and dose expansion study of SQZ PBMC HPV as monotherapy and in combination with atezolizumab in HLA-A*02+ Patients with HPV16+ recurrent, or metastatic solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A444-A444
Author(s):  
Cathy Eng ◽  
Joaquina Baranda ◽  
Matthew Taylor ◽  
Michael Gordon ◽  
Ursula Matulonis ◽  
...  
Keyword(s):  
T Cell ◽  
Solid Tumors ◽  
Cancer Vaccine ◽  
Phase 1 ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Dose Effect ◽  
Statistical Hypothesis ◽  
Mhc I ◽  
Cell Responses

BackgroundSQZ-PBMC-HPV is a therapeutic cancer vaccine created with Cell Squeeze®, a proprietary cell-engineering system. SQZ-PBMC-HPV is a novel cancer vaccine generated from peripheral blood mononuclear cells (PBMC) squeezed with HPV16 E6 and E7 antigens, resulting in delivery into the cytosol. The resulting antigen presenting cells (APCs) provide enhanced antigen presentation on MHC-I to potentially elicit robust, antigen-specific CD8+ T cell responses. Importantly, SQZ-PBMC-HPV are neither genetically modified nor immune effector cells.Studies in MHC-I knockout mice demonstrated that activation of antigen specific CD8+ tumor infiltrating lymphocytes (TILs) was a direct effect of cytosolic antigen delivery to PBMCs. In the murine TC-1 tumor model, tumor regression correlated with an influx of HPV16-specific CD8+ TILs. In vitro studies with human volunteer PBMCs demonstrated that each subset is capable of inducing CD8+ T cell responses. The Phase 1 study includes a significant biomarker program to investigate whether pharmacodynamic effects observed in non-clinical studies correlate with potential clinical benefit. Immunogenic and pharmacodynamic endpoints include Elispot assays to measure frequency of interferon gamma secreting cells, as well as quantification and characterization of TILs and tumor microenvironment. In addition, various cytokine responses and circulating cell-free HPV16 DNA levels in plasma are measured.MethodsSQZ-PBMC-HPV-101 (NCT04084951) is open for enrollment to HLA A*02+ patients with HPV16+ recurrent, locally advanced or metastatic solid tumors and includes escalation cohorts for monotherapy and in combination with atezolizumab. After initial demonstration of safety, the study assesses dose effect by testing different cell dose levels, the effect of prolonged antigen priming in Cycle 1 [APC administration on Day 1 only compared to Days 1 and 2 (double priming)] and the impact of treatment duration to identify the optimal dose regimen. The cycle length is 3 weeks, and patients will receive SQZ-PBMC-HPV for up to 1 year or until available autologous drug product is exhausted. Atezolizumab will be administered for up to 1 year. Eligible patients including but not limited to anal, cervical and head and neck tumors will undergo a single leukapheresis at the study site. The manufacturing process includes a maturation step and takes less than 24 hours. The vein-to-vein time for the 1st administration is approximately one week. Patients must have a lesion that can be biopsied with acceptable clinical risk and agree to have a fresh biopsy at Screening and on study. A Study Safety Committee is in place. No formal statistical hypothesis testing will be performed.ResultsN/AConclusionsN/ATrial RegistrationNCT04084951Ethics ApprovalThe study is registered on clinicaltrials.gov was approved by the Ethics Board of all institution listed as recruiting.

Identification of CD8+ T-cell Epitopes that Associate with Distinct Functionality, Proliferation and Polyfunctionality

2014 ◽  
Vol 30 (S1) ◽  
pp. A175-A175
Author(s):  
Meika EI Richmond ◽  
Sandra A. Kiazyk ◽  
Lyle R. Mckinnon ◽  
Billy Nyanga ◽  
Charles Wachihi ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Epitopes

High-throughput Screening for CD8+ T Cell Epitopes Targeted in Type 1 Diabetes

2010 ◽  
Vol 135 ◽  
pp. S19
Author(s):  
Brian Hondowicz ◽  
Katharine Schwedhelm ◽  
Arnold Kas ◽  
Michael Tasch ◽  
Nirasha Ramchurren ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cd8 T Cell ◽  
T Cell Epitopes

scholarly journals Extensive Polymorphism and Evidence of Immune Selection in a Highly Dominant Antigen Recognized by Bovine CD8 T Cells Specific for Theileria annulata

2011 ◽  
Vol 79 (5) ◽  
pp. 2059-2069 ◽  
Author(s):  
Niall D. MacHugh ◽  
William Weir ◽  
Alison Burrells ◽  
Regina Lizundia ◽  
Simon P. Graham ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Theileria Annulata ◽  
T Cell Epitopes ◽  
Major Histocompatibility Complex Haplotype ◽  
Content Type ◽  
Cell Responses ◽  
Restricted Epitope

ABSTRACTAlthough parasite strain-restricted CD8 T cell responses have been described for several protozoa, the precise role of antigenic variability in immunity is poorly understood. The tick-borne protozoan parasiteTheileria annulatainfects leukocytes and causes an acute, often fatal lymphoproliferative disease in cattle. Building on previous evidence of strain-restricted CD8 T cell responses toT. annulata, this study set out to identify and characterize the variability of the target antigens. Three antigens were identified by screening expressed parasite cDNAs with specific CD8 T cell lines. In cattle expressing the A10 class I major histocompatibility complex haplotype, A10-restricted CD8 T cell responses were shown to be focused entirely on a single dominant epitope in one of these antigens (Ta9). Sequencing of the Ta9 gene from field isolates ofT. annulatademonstrated extensive sequence divergence, resulting in amino acid polymorphism within the A10-restricted epitope and a second A14-restricted epitope. Statistical analysis of the allelic sequences revealed evidence of positive selection for amino acid substitutions within the region encoding the CD8 T cell epitopes. Sequence differences in the A10-restricted epitope were shown to result in differential recognition by individual CD8 T cell clones, while clones also differed in their ability to recognize different alleles. Moreover, the representation of these clonal specificities within the responding CD8 T cell populations differed between animals. As well as providing an explanation for incomplete protection observed after heterologous parasite challenge of vaccinated cattle, these results have important implications for the choice of antigens for the development of novel subunit vaccines.

Sign in / Sign up

Export Citation Format

Share Document