GTOnco™ Platform for Gene Therapy-based I-O Drug Development

Immuno-oncology (I-O) drug development is a growing and young field on the frontier of immunotherapy, marked by stimulating the body's immune system to target and attack the pathogens. Gene therapy is recognized as the most prominent approach enabling effective I-O strategies and has become a driver of innovation in the I-O field, enabling drug discovery, novel target definitions and validation.

Creative Biolabs manifests as a world-leading expert in immunotherapy and our extensive expertise in I-O drugs development spans all phases, from prove-of-concept assays to Investigational New Drug (IND) application. Relying on our well-established GTOnco™ platform, both routine and custom designed assays can be provided to meet your drug development program.

On the basis of mechanisms underlining immuno-oncology therapy and current studies, our GTOnco™ platform offers gene therapy-based I-O drugs development as follows:

Figure 1. T-cell targets for immunotherapy. (Marshall, 2018)

Reversing the Inhibition of Adaptive Immunity

Although the immune system has a milieu of inhibitory receptors to limit excessive T cell-mediated inflammatory responses, cancer cells have evolved to seize those inhibitory pathways and to prevent T cell-mediated killing of tumor cells. Therefore, immune checkpoint inhibitors (ICI) are consisted of blocking antibodies against these receptors and have been promising means of inhibiting immune system tolerance to tumors and thus rescue exhausted antitumor T cells. At Creative Biolabs, we have developed streamlined protocols for efficient delivery of ICI agents by viral vectors. Various vectors have been engineered to express antibodies targeting CTLA-4, PD1, PD-L1 or Tim3, etc. GTOnco™ platform also provides preclinical validation of the recombinant immuno-oncology products.

Switching on Adaptive Immunity

The immuno-modulatory cytokines such as IL-15 and IL-21 show significant potential for stimulating anti-tumor T lymphocytes and NK cells. In addition, the agonist ligands of CD40 and OX40 also play a central role in co-stimulation and regulation of the immune response. Recombinant viral vectors encoding those cytokines and agonist ligands have been created that showed superior anti-tumor activity in vitro and in vivo. Based on our advanced GTOnco™ platform, Creative Biolabs offers the custom services to help our clients to design the gene therapy-based I-O products armed with various immuno-modulatory cytokines and agonist ligands. Of course, the potency and safety test of I-O drugs are also available in GTOnco™ platform and multiple assays could be selected to meet your project.

Expanding Adaptive Immunity

Adoptive cell transfer (ACT) is a promising approach to enhance and expand the adaptive immunity. It involves the removal of T-cells from the body, which are then expanded and genetically modified for specificity toward tumor-associated antigens (TAAs), and then reintroduced to the patient. In ACT therapy, redirection of antigen-specificity is usually based on either a TCR of known specificity or a synthetic receptor such as a chimeric antigen receptor (CAR). At Creative Biolabs, T lymphocytes can be modified by gene transfer methods to permanently or transiently express therapeutic genes to enhance and expand the therapies. GTOnco™ platform offers a broad range of novel assays for assessment of the functional activity of ACT modalities in gene therapy.

Figure 2. The two methods of genetically modified ACT. (Kamta, 2017)

Activating the Immune System

Figure 3. Cytokine-expressing OVs modulate tumor microenvironment. (Pearl, 2019)

The use of engineered oncolytic viruses (OVs) and cancer vaccine to activate the immune system has shown satisfactory progress. OVs are genetically modified natural viruses for selectivity toward tumor cells. The resulting cytotoxicity has the potential to elicit an immune response that furthers leads to tumor cell killing. Vaccine-based immunotherapy using tumor antigen infusion enhances the innate anti-tumor ability of a patient's immune system. GTOnco™ platform provides the immune stimulator-expressing OVs and engineered vaccine to activate the immune system. Several robust animal models and assay systems have been used in-house to greatly facilitate I-O drugs development.

Creative Biolabs is a world-renowned life science service provider that has extensive experience in preclinical stage development of gene therapy-based I-O drugs discovery. GTOnco™ platform is dedicated to providing the best-characterized assays for validation of I-O products. We are committed to working with clients through every step of the process to streamline preclinical programs, determine the optimal outsourcing strategy. If you are interested in our service, please contact us by E-mail.

References

1. Kamta, J.; et al. (2017). Advancing Cancer Therapy with Present and Emerging Immuno-Oncology Approaches. Frontiers in Oncology. 7.
2. Marshall, H. and Djamgoz, M. (2018). Immuno-Oncology: Emerging Targets and Combination Therapies. Frontiers in Oncology. 8.
3. Pearl, T.; et al. (2019). Oncolytic Virus-Based Cytokine Expression to Improve Immune Activity in Brain and Solid Tumors. Molecular Therapy - Oncolytics, 13, pp.14-21.