scholarly journals Radiation Therapy Combined with Cowpea Mosaic Virus Nanoparticle in Situ Vaccination Initiates Immune-Mediated Tumor Regression

ACS Omega ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 3702-3707 ◽  
Author(s):  
Ravi Patel ◽  
Anna E. Czapar ◽  
Steven Fiering ◽  
Nancy L. Oleinick ◽  
Nicole F. Steinmetz
2018 ◽  
Vol 5 (5) ◽  
pp. 1700991 ◽  
Author(s):  
Anna E. Czapar ◽  
Brylee David B. Tiu ◽  
Frank A. Veliz ◽  
Jonathan K. Pokorski ◽  
Nicole F. Steinmetz

2015 ◽  
Vol 11 (3) ◽  
pp. 295-303 ◽  
Author(s):  
P. H. Lizotte ◽  
A. M. Wen ◽  
M. R. Sheen ◽  
J. Fields ◽  
P. Rojanasopondist ◽  
...  

2021 ◽  
Author(s):  
Paul L. Chariou ◽  
Veronique Beiss ◽  
Yifeng Ma ◽  
Nicole F. Steinmetz

Cowpea mosaic virus (CPMV) is currently in the development pipeline for multiple biomedical applications, including cancer immunotherapy.


2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi138-vi138
Author(s):  
Amber Kerstetter-Fogle ◽  
Sourabh Shukla ◽  
Veronique Beiss ◽  
Peggy Harris ◽  
Andrew Sloan ◽  
...  

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Chao Wang ◽  
Veronique Beiss ◽  
Nicole F. Steinmetz

ABSTRACT Cowpea mosaic virus (CPMV) is a plant virus that has been developed for multiple biomedical and nanotechnology applications, including immunotherapy. Two key platforms are available: virus nanoparticles (VNPs) based on the complete CMPV virion, including the genomic RNA, and virus-like nanoparticles (VLPs) based on the empty CPMV (eCPMV) virion. It is unclear whether these platforms differ in terms of immunotherapeutic potential. We therefore compared their physicochemical properties and immunomodulatory activities following in situ vaccination of an aggressive ovarian tumor mouse model (ID8-Defb29/Vegf-A). In physicochemical terms, CPMV and eCPMV were very similar, and both significantly increased the survival of tumor-bearing mice and showed promising antitumor efficacy. However, they demonstrated distinct yet overlapping immunostimulatory effects due to the presence of virus RNA in wild-type particles, indicating their suitability for different immunotherapeutic strategies. Specifically, we found that the formulations had similar effects on most secreted cytokines and immune cells, but the RNA-containing CPMV particles were uniquely able to boost populations of potent antigen-presenting cells, such as tumor-infiltrating neutrophils and activated dendritic cells. Our results will facilitate the development of CPMV and eCPMV as immunotherapeutic vaccine platforms with tailored responses. IMPORTANCE The engagement of antiviral effector responses caused by viral infection is essential when using viruses or virus-like particles (VLPs) as an immunotherapeutic agent. Here, we compare the chemophysical and immunostimulatory properties of wild-type cowpea mosaic virus (CPMV) (RNA containing) and eCPMV (RNA-free VLPs) produced from two expression systems (agrobacterium-based plant expression system and baculovirus-insect cell expression). CPMV and eCPMV could each be developed as novel adjuvants to overcome immunosuppression and thus promote tumor regression in ovarian cancer (and other tumor types). To our knowledge, this is the first study to define the immunotherapeutic differences between CPMV and eCPMV, which is essential for the further development of biomedical applications for plant viruses and the selection of rational combinations of immunomodulatory reagents.


2020 ◽  
Vol 8 (19) ◽  
pp. 5489-5503
Author(s):  
Sourabh Shukla ◽  
Chao Wang ◽  
Veronique Beiss ◽  
Hui Cai ◽  
Torus Washington ◽  
...  

Plant viral nanoparticle CPMV outperforms other icosahedral viruses as an in situ vaccine for cancer immunotherapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ye Wang ◽  
Morvarid Mohseni ◽  
Angelo Grauel ◽  
Javier Estrada Diez ◽  
Wei Guan ◽  
...  

AbstractSHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.


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