scholarly journals Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Sandra M. Kallert ◽  
Stephanie Darbre ◽  
Weldy V. Bonilla ◽  
Mario Kreutzfeldt ◽  
Nicolas Page ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Vector ◽  
Cd8 T Cell ◽  
Tumour Immunotherapy

scholarly journals EXTH-51. GENETICALLY STABLE POLIOVIRUS VECTOR PLATFORM FOR DIPG IMMUNOTHERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi93-vi93
Author(s):  
Matthias Gromeier ◽  
Mubeen Mosaheb ◽  
Elena Dobrikova ◽  
Michael Brown ◽  
Darell Bigner ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Vector ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Anatomical Location ◽  
Cell Responses ◽  
Cell Immunity

Abstract Options for the immunotherapy of diffuse intrinsic pontine glioma (DIPG), due to its anatomical location and inherent therapy resistance, are limited. The histone 3.3(K27M) mutation in ~80% of such tumors offers a unique opportunity for immunotherapy intervention, as it defines a high affinity, HLA-A2-restricted tumor neoantigen that spontaneously elicits CD8+ T cell responses in DIPG patients. Immunizing against the H3.3(K27M) signature in the clinic has been challenging, as conventional approaches (i.e. peptide-conjugates administered with adjuvants) lack the costimulatory signals known to drive CD8+ effector T cell responses. Therefore, we built on a viral vector approach for engaging innate immune responses to virus infection specifically in antigen presenting cells. Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. We devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in syngeneic rodent tumor models. We are preparing a prototype PVSRIPO-derived vector delivering the H3.3(K27M) signature for clinical investigation.

scholarly journals Promising Cytomegalovirus-Based Vaccine Vector Induces Robust CD8+ T-Cell Response

2019 ◽  
Vol 20 (18) ◽  
pp. 4457 ◽  
Author(s):  
Jian Liu ◽  
Dabbu Kumar Jaijyan ◽  
Qiyi Tang ◽  
Hua Zhu
Keyword(s):  
T Cell ◽  
Viral Vector ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Effector Memory ◽  
Great Success ◽  
Cell Responses ◽  
Viral Vaccine

Vaccination has had great success in combating diseases, especially infectious diseases. However, traditional vaccination strategies are ineffective for several life-threatening diseases, including acquired immunodeficiency syndrome (AIDS), tuberculosis, malaria, and cancer. Viral vaccine vectors represent a promising strategy because they can efficiently deliver foreign genes and enhance antigen presentation in vivo. However, several limitations, including pre-existing immunity and packaging capacity, block the application of viral vectors. Cytomegalovirus (CMV) has been demonstrated as a new type of viral vector with additional advantages. CMV could systematically elicit and maintain high frequencies of effector memory T cells through the “memory inflation” mechanism. Studies have shown that CMV can be genetically modified to induce distinct patterns of CD8+ T-cell responses, while some unconventional CD8+ T-cell responses are rarely induced through conventional vaccine strategies. CMV has been used as a vaccine vector to deliver many disease-specific antigens, and the efficacy of these vaccines was tested in different animal models. Promising results demonstrated that the robust and unconventional T-cell responses elicited by the CMV-based vaccine vector are essential to control these diseases. These accumulated data and evidence strongly suggest that a CMV-based vaccine vector represents a promising approach to develop novel prophylactic and therapeutic vaccines against some epidemic pathogens and tumors.

scholarly journals Cutting Edge: A Potent Adjuvant Effect of Ligand to Receptor Activator of NF-κB Gene for Inducing Antigen-Specific CD8+ T Cell Response by DNA and Viral Vector Vaccination

2003 ◽  
Vol 171 (12) ◽  
pp. 6344-6348 ◽  
Author(s):  
Yasushi Miyahira ◽  
Hisaya Akiba ◽  
Masaharu Katae ◽  
Kaori Kubota ◽  
Seiki Kobayashi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Viral Vector ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cutting Edge ◽  
Adjuvant Effect ◽  
Receptor Activator

scholarly journals Orf Virus-Based Vaccine Vector D1701-V Induces Strong CD8+ T Cell Response against the Transgene but Not against ORFV-Derived Epitopes

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 295 ◽  
Author(s):  
Alena Reguzova ◽  
Michael Ghosh ◽  
Melanie Müller ◽  
Hanns-Joachim Rziha ◽  
Ralf Amann
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cellular Immunity ◽  
Cell Response ◽  
Vaccine Development ◽  
Viral Vector ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Specific Immune Response ◽  
Orf Virus

The potency of viral vector-based vaccines depends on their ability to induce strong transgene-specific immune response without triggering anti-vector immunity. Previously, Orf virus (ORFV, Parapoxvirus) strain D1701-V was reported as a novel vector mediating protection against viral infections. The short-lived ORFV-specific immune response and the absence of virus neutralizing antibodies enables repeated immunizations and enhancement of humoral immune responses against the inserted antigens. However, only limited information exists about the D1701-V induced cellular immunity. In this study we employed major histocompatibility complex (MHC) ligandomics and immunogenicity analysis to identify ORFV-specific epitopes. Using liquid chromatography-tandem mass spectrometry we detected 36 ORFV-derived MHC I peptides, originating from various proteins. Stimulated splenocytes from ORFV-immunized mice did not exhibit specific CD8+ T cell responses against the tested peptides. In contrast, immunization with ovalbumin-expressing ORFV recombinant elicited strong SIINFEKL-specific CD8+ T lymphocyte response. In conclusion, our data indicate that cellular immunity to the ORFV vector is negligible, while strong CD8+ T cell response is induced against the inserted transgene. These results further emphasize the ORFV strain D1701-V as an attractive vector for vaccine development. Moreover, the presented experiments describe prerequisites for the selection of T cell epitopes exploitable for generation of ORFV-based vaccines by reverse genetics.

Author response for "CXCR4, but not CXCR3, drives CD8 T-cell entry into and migration through the murine bone marrow"

2018 ◽  
Author(s):  
Marieke Goedhart ◽  
Stephanie Gessel ◽  
Robbert van der Voort ◽  
Edith Slot ◽  
Beth Lucas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cd8 T Cell ◽  
Cell Entry ◽  
Author Response ◽  
Murine Bone Marrow ◽  
And Migration
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