Oncolytic Virotherapy Development for Combination Therapy with Immune Checkpoint Inhibitors
Oncolytic virotherapy is a therapeutic approach to cancer treatment that utilizes native or genetically modified viruses that selectively replicate within tumor cells. As a standalone therapy, the overall efficacy of OVs is prone to be decreased due to the tumor microenvironment, anti-viral response as well as neutralizing antibodies. Preclinical studies have confirmed that the objective response rates can increase and have tolerable safety profiles when oncolytic viruses are used in combination with immune checkpoint inhibitors. With extensive experience in oncolytic virotherapy and immunotherapy, Creative Biolabs provides one-stop services of combination immunotherapy covering all aspects of preclinical investigation for clients worldwide.
Immune checkpoint inhibitors (ICIs) aim to overcome tumor-induced immune suppression and evasion caused by the expression of immune checkpoints. Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death 1 (PD1) are two well-studied immune checkpoint molecules. The combination therapies of ICIs and OVs are attractive, as OVs has the ability to increase T cell recruitment and promote immune cell activation by triggering the release of soluble tumor antigens, danger signals and pro-inflammatory cytokines. Scientists in Creative Biolabs have developed various of ICIs and built different combination therapy platform which are potentially suitable to combine with multiple OVs. We focus on applying outstanding technologies to develop potential cancer therapeutic approaches.
Our combination of oncolytic virotherapy and immune checkpoint inhibitors services include but not limited to:
Assay Development for OVs Combined with ICIs
A number of preclinical studies show that ICIs can increase the efficacy of OV therapy involving a variety of viral platforms. By blocking the PD1/PDL1 pathway, therapeutic antibodies nivolumab (Opdivo), pembrolizumab (Keytruda), atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio), can block a protective mechanism of cancer cells and augment the anti-tumor immune response. Similarly, blocking antibody ipilimumab (Yervoy) targeting CTLA-4 pathway. We provide various cell lines and animal models to be applied to researches both in vivo and in vitro that will suit your needs.
- In vivo
C57/BL6 and BALB/c female mice
C57BL/6 mice with subcutaneous B16-CD20 tumors
Derived from murine models of human cancer.
Fully immunocompetent murine model of malignant melanoma (B16-CD20).
Immunocompetent mouse models of renal and colorectal cancer.
Mice with glioblastoma stem cell (GSC)-derived tumors
NOD/SCID mice with subcutaneous Mel888 tumors
Syngeneic EMT6 murine model of BrCa
- In vitro
Human and murine BrCa cell lines
Subcutaneous B16 melanoma model
Mouse syngeneic GSC tumor model
MV-sensitive melanoma model
Primary human cancer cells
Renca (murine renal adenocarcinoma) cell line
Arming Oncolytic Virus with ICIs Payload
The combined use of antibodies to CTLA4 and PD1 has demonstrated increased efficacy compared with antibody alone, but it brings substantially increased toxicity to patients and cost to health-care systems. Engineering OVs to encode ICIs potentially reduces the need for combination therapies. The exquisite selectivity of OVs for cancer cells can lead to localized production of ICIs, which in turn can provide a superior safety profile to systemic administration. This also creates an attractive niche for strategies that combining multiple ICIs in a single therapeutic agent, and ensuring that the OVs reaches every relevant anatomical site to achieve the desired effect.
- Armed the adenovirus encoding anti-CTLA-4 in prostate and lung cancer xenograft enhanced the oncolytic efficacy.
- Armed the oncolytic vaccinia virus with soluble forms of PD-1-blocking antibodies to locally induce anti-PD-1 inhibition in tumor which can augment antitumor efficacy in a murine fibrosarcoma model.
- Armed myxoma virus expressing a soluble PD-1-blocking antibody to restrict PD-1 inhibition to the tumor and to reduce systemic autoimmune-like toxicity.
- Armed the measles virus expressing antibody against PD-L1 (MV-aPD-L1) and CTLA-4 (MV-aCTLA-4), which improved antitumor efficacy and decreased the presence of tumour in a murine melanoma model.
Creative Biolabs has long-term devoted to the development and application of immune checkpoint inhibitors and oncolytic virotherapy. Our scientists develop specific oncolytic viruses to combine with different types of ICIs to improve the effectiveness of cancer treatment which can meet your research demands both in vitro and in vivo. We also offer various auxiliary diagnostic assay kits to determine the expression level of PD-L1 in tumor infiltrating immune cells to search for rationally combination strategies. Please feel free to contact us for more details and our scientists will tailor the most reasonable scheme for your projects, we will be pleased to serve you.
References:
- Twumasi-Boateng, K., Pettigrew, J. L., Kwok, Y. E., Bell, J. C., & Nelson, B. H. (2018). Oncolytic viruses as engineering platforms for combination immunotherapy. Nature Reviews Cancer, 1.
- Chen, C. Y., Hutzen, B., Wedekind, M. F., & Cripe, T. P. (2018). Oncolytic virus and PD-1/PD-L1 blockade combination therapy. Oncolytic virotherapy, 7, 65.
- Engeland, C. E., Grossardt, C., Veinalde, R., Bossow, S., Lutz, D., Kaufmann, J. K., ... & Jäger, D. (2014). CTLA-4 and PD-L1 checkpoint blockade enhances oncolytic measles virus therapy. Molecular Therapy, 22(11), 1949-1959.