scholarly journals 61. Higher In Vivo Maintenance, Biodistribution and Immunopotency of Dendritic Cell Vaccines Self-Differentiated through Lentiviral Vector Programming

2005 ◽  
Vol 11 ◽  
pp. S25
2007 ◽  
Vol 15 (5) ◽  
pp. 971-980 ◽  
Author(s):  
Richard C Koya ◽  
Takahiro Kimura ◽  
Antoni Ribas ◽  
Nora Rozengurt ◽  
Gregory W Lawson ◽  
...  

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi99-vi99
Author(s):  
Vrunda Trivedi ◽  
Changlin Yang ◽  
Oleg Yegorov ◽  
Kyle Dyson ◽  
Duane Mitchell

Abstract BACKGROUND Glioblastoma multiforme (GBM) remains a disease with debilitating survival outcomes. Owing to the heterogeneous nature and low mutation burden, identifying multiple antigens inherent to GBM that may serve as targets for immune-based therapies is attractive. Our aim is to develop a personalized immunotherapy approach using cancer immunogenomics for prospectively identifying neoantigens and uniquely expressed tumor proteins and then selectively expanding T cells against these truly tumor-specific antigens and dendritic cell vaccines to boost the T cell responses. METHODS RNAseq and WES was performed for murine KR158-luc GBM tumor. Using a cancer immunogenomics approach that we developed, called the O pen R eading Frame A ntigen N etwork (O.R.A.N.), we identified the immunogenic neoantigens and tumor-associated antigens (TAAs) including cancer testis and developmental antigens, that are aberrantly over-expressed in KR158-luc tumor. All predicted genes were subjected to a gene enrichment strategy and an mRNA library was generated containing predominantly only the target genes but had some background non-specific genes (validated by RNAseq). KR158-luc tumor bearing animals were then treated with dendritic cells loaded with the tumor antigen specific mRNA library. Tumor volume and thus progress was determined using in vivo luciferase imaging technique. Additionally, tetramers specific to several of the predicted antigens were manufactured and the frequency of antigen specific T cells was determined using flow cytometry. RESULTS The dendritic cell vaccines were effective in delaying the progression of KR158-luc tumors and we identified T cells targeting several of our predicted antigens in the tumor bearing animals. The antigen specific T cells were detected in the tumor infiltrating lymphocytes as well as in the peripheral lymph organs. CONCLUSION We developed a dendritic cell-based vaccination approach targeting all neoantigens and TAAs identified as being tumor-specific and validated our developed immunogenomics pipeline by identifying antigen-specific T cells in the tumor bearing animals against novel GBM antigens.


2014 ◽  
Vol 14 (5) ◽  
pp. 365-376 ◽  
Author(s):  
Abarrategui-Pontes Cecilia ◽  
Creneguy Alison ◽  
Thinard Reynald ◽  
Fine J. ◽  
Thepenier Virginie ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1288
Author(s):  
Wendy Dong ◽  
Boris Kantor

CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector’s expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.


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