scholarly journals Harnessing the Potential of Combination Immunotherapy and Oncolytic Virotherapy for Solid Tumors

2021 ◽  
Author(s):  
Sonia Cohen ◽  
Genevieve M. Boland
Keyword(s):  
Solid Tumors ◽  
Oncolytic Virotherapy ◽  
Combination Immunotherapy

scholarly journals Combination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors

Cancer Cell ◽  
2019 ◽  
Vol 36 (5) ◽  
pp. 471-482 ◽  
Author(s):  
Rachel Grosser ◽  
Leonid Cherkassky ◽  
Navin Chintala ◽  
Prasad S. Adusumilli
Keyword(s):  
T Cells ◽  
Solid Tumors ◽  
Checkpoint Blockade ◽  
Combination Immunotherapy ◽  
Car T Cells ◽  
Car T

scholarly journals Optimal Individualized Combination Immunotherapy/Oncolytic Virotherapy Determined ThroughIn SilicoClinical Trials Improves Late Stage Melanoma Patient Outcomes

2019 ◽  
Author(s):  
Tyler Cassidy ◽  
Morgan Craig
Keyword(s):  
Patient Outcomes ◽  
Late Stage ◽  
Oncolytic Virotherapy ◽  
Great Promise ◽  
Combination Immunotherapy ◽  
Gm Csf ◽  
Exogenous Cytokine ◽  
Interdisciplinary Approaches ◽  
Macrophage Colony ◽  
Simplex Virus

AbstractOncolytic virothcrapics, including the modified herpes simplex virus talimogene laherparepvec (T-VEC), have shown great promise as potent instigators of anti-tumour immune effects. The OPTiM trial in particular demonstrated the superior anti-cancer effects of T-VEC as compared to more traditional immunotherapy treatment using exogenous administration of granulocyte-macrophage colony-stimulating factor (GM-CSF). Theoretically, a combined approach leveraging immunotherapies: like exogenous cytokine administration and oncolytic virotherapv would elicit an even greater immune response and improve patient outcomes, but given that their efficacy and safety must be tested in large clinical trials, combination therapeutic regimens have yet to be established. By adopting computational biology andin silicoclinical trial approaches, here we show significantly improved patient outcomes for individuals with late-stage melanoma by personalizing and optimizing combination oncolytic, virotherapv and GM-CSF therapy. Our results serve as a proof-of-concept, for interdisciplinary approaches to determining combination therapy, and suggest promising avenues of investigation towards tailored combination immunotherapy/oncolytic virotherapy.

scholarly journals Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors

2020 ◽  
Vol 12 (559) ◽  
pp. eaaz1863 ◽  
Author(s):  
Anthony K. Park ◽  
Yuman Fong ◽  
Sang-In Kim ◽  
Jason Yang ◽  
John P. Murad ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
De Novo ◽  
Oncolytic Viruses ◽  
Combination Immunotherapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Chimeric antigen receptor (CAR)–engineered T cell therapy for solid tumors is limited by the lack of both tumor-restricted and homogeneously expressed tumor antigens. Therefore, we engineered an oncolytic virus to express a nonsignaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-CAR T cells. Infecting tumor cells with an oncolytic vaccinia virus coding for CD19t (OV19t) produced de novo CD19 at the cell surface before virus-mediated tumor lysis. Cocultured CD19-CAR T cells secreted cytokines and exhibited potent cytolytic activity against infected tumors. Using several mouse tumor models, delivery of OV19t promoted tumor control after CD19-CAR T cell administration. OV19t induced local immunity characterized by tumor infiltration of endogenous and adoptively transferred T cells. CAR T cell–mediated tumor killing also induced release of virus from dying tumor cells, which propagated tumor expression of CD19t. Our study features a combination immunotherapy approach using oncolytic viruses to promote de novo CAR T cell targeting of solid tumors.

scholarly journals Effective Combination Immunotherapy using Oncolytic Viruses to Deliver CAR Targets to Solid Tumors

2019 ◽  
Author(s):  
Anthony K. Park ◽  
Yuman Fong ◽  
Nanhai G. Chen ◽  
Brook Jeang ◽  
Dileshni Tilakawardane ◽  
...  
Keyword(s):  
T Cell ◽  
Solid Tumors ◽  
De Novo ◽  
Oncolytic Viruses ◽  
Combination Immunotherapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Effective Combination ◽  
Car T ◽  
Tumor Expression

AbstractChimeric antigen receptor (CAR)-engineered T cell therapy for solid tumors is limited by the lack of tumor-restricted and homogeneous expression of tumor antigens1,2. Therefore, we engineered an oncolytic virus to express a non-signaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-specific CAR T cells. Infecting tumor cells with a chimeric oncolytic vaccinia virus coding for CD19t (OV19t) produced de novo CD19 surface-antigen expression prior to virus-mediated tumor lysis. Co-cultured CD19-CAR T cells secreted cytokines and elicited potent cytolytic activity against infected tumors. Using multiple mouse tumor models, intratumoral delivery of OV19t induced tumor expression of CD19t and improved tumor control following CD19-CAR T cell administration. CAR T cell–mediated tumor killing also promoted release of virus from dying tumor cells, which propogated tumor expression of CD19t. These data demonstrate a novel immunotherapy approach utilizing oncolytic viruses to promote de novo CAR T cell targeting of solid tumors.One Sentence SummaryWe describe a novel and effective combination immunotherapy utilizing oncolytic viruses to deliver de novo cell surface expression of CD19 antigen promoting CD19-CAR T cell anti-tumor responses against solid tumors.

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