Oncolytic Virotherapy Development for Combination Therapy with Cytokines
Oncolytic virotherapy is an approach either with natural tropism for neoplastic cells or genetically modified to enhance selectivity of tumor cells. Recently, the focus on the oncolytic virotherapy field has shifted from oncolytic efficacy to immune stimulatory effect. Noncellular therapies for combination with OV therapy intend to restore the intratumoral balance of cytokines and chemokines into a more favorable inflammatory TME to attract and activate immune cells. With extensive experience in combination therapy of oncolytic virus armed with cytokines, Creative Biolabs provides one-stop services for a broad range of project objectives.
Immunotherapy for treatment of cancer aims at overcoming the tumor immune suppressive environment and increasing antitumor immunity. One of the first immune therapeutic approaches in cancer treatment is the administration of recombinant cytokines. Cytokines, encoded by small genes and in general easy to build in oncolytic viral genomes, are key players in stimulating and regulating antitumor immune responses. Moreover, they have pleiotropic effects on targeting different immune cells simultaneously. By introducing cytokines in oncolytic viral vectors, adverse events can be reduced, resistance reverted and treatment responsiveness enhanced. The most essential cytokines are IL-12, GM-CSF and IL-2, and they all stimulate different parts of the immune system.
Our combination of oncolytic virotherapy and cytokines services include but not limited to:
Colony-stimulating Factors (CSFs)
Granulocyte–macrophage colony-stimulating factor (GM-CSF) is the most extensively studied cytokine. GM-CSF produced by engineered oncolytic viruses recruits DCs to sites of tumor cell, resulting the stimulation of DCs maturation of. Currently, many oncolytic viruses such as HSV, AdV, MV, VSV and NDV have been armed with GM-CSF to treat adenocarcinoma, metastatic breast cancer and melanoma.
Interferons (IFNs)
- Type I interferon
IFN-α/β is not only important in antiviral responses, but also plays a role in anti-cancer immunity by inducing DC maturation and CTL and NK cell activation. Combined with MV, VV VSV and NDV, IFN-β can treat non-small cell lung cancer, mesothelioma and pancreatic adenocarcinoma.
- Type II interferon
IFN-γ is an important Th1 effector cytokine, secreted by activated Th1 cells, CTLs and NK cells. A recent study suggested that IFN-γ induces a stronger immune response by upregulates MHC I expression in tumor cells. IFN-γ has also combined with NDV and VSV that can be applied to melanoma and mammary and colon carcinoma.
Interleukin (IL)
- IL-2 and IL-15
IL-2 is a T cell growth factor and improves T cell expansion. Local delivery of IL-2 by OVs can reduce tumor growth and increase T cell infiltration of the tumors. The combination of IL-2 with NDV or HSV can be applied to cancer treatment of melanoma, hepatoma and squamous cell carcinoma.
IL-15 can stimulate NK and effector T-cells and has indicated that treatment with OVs expressing IL-15 is more efficient than systemic treatment with IL-15. IL-15 has combined with VSV, HSV and NDV to treat colon carcinoma and melanoma.
- IL-12
IL-12 is normally expressed by APCs and stimulates polarization of T helper cells to a Th1 phenotype. Several viruses like AdV, HSV and VSV have been armed with IL-12 and tested in different tumor models of neuroblastoma, glioma, prostate, squamous cell carcinoma and melanoma.
Tumor Necrosis Factor (TNF)
It is reported that tumor necrosis factor (TNFα) -armed oncolytic virus for instance HSV, VSV, AdV and DNV can enhance adoptive cell therapy by favorable alteration of the tumor microenvironment.
Chemokines
Important chemokines in the TME are CCL2, CCL5, CXCL9 and CXCL10. It has shown that the combination of OV therapy with chemokines efficiently increased the infiltration of T cells into the tumor and thus improve antitumor efficacy. Chemokines has been successfully used to arm HSV and VV for treatment of colon carcinoma.
Based on advanced technology and years of experience in oncolytic virotherapy study, Creative Biolabs provides several oncolytic viruses that have been engineered to express different cytokines or chemokines which are potentially suitable to our clients' requirements. Scientists of Creative Biolabs focus on applying different combinations of OVs and cytokines to prolong patient survival and hence the additive effect. Not only do we own one of the world's most comprehensive cytokines products and research techniques, but also offer the most suitable scheme on the basis of your research demand. We are pleased to greatly assist with your researches and preclinical investigations of cancer therapy development.
References:
- Bommareddy, P. K., Shettigar, M., & Kaufman, H. L. (2018). Integrating oncolytic viruses in combination cancer immunotherapy. Nature Reviews Immunology, 1.
- de Graaf, J. F., de Vor, L., Fouchier, R. A. M., & van den Hoogen, B. G. (2018). Armed oncolytic viruses: A kick-start for anti-tumor immunity. Cytokine & growth factor reviews.