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Development of therapeutic cancer vaccines against various tumor antigens

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1 Purpose

Nykode Therapeutics ASA is dedicated to the discovery and development of novel cancer vaccines. Nykode has developed a versatile vaccine platform using its proprietary NeoSELECT™ bioinformatics platform to identify the broad class of cancer antigens derived from somatic mutations in cancer cell genomes. The purpose of this experiment is to assess the type of T cell responses (CD4+ and/or CD8+ T cell-mediated) elicited against the different class of tumor antigens obtained from four different mice tumor cell lines. We prime vaccinate the mice once followed by multiple boost vaccination regimes with Nykode's plasmid vaccine encoding the selected class of tumor antigens in various combinations. To increase transfection efficiency and vaccine responses, we will make use of the adjuvant Hyaluronidase. The T cell-mediated immune responses will be measured in the spleen using the enzyme-linked immune absorbent spot (ELISpot) and Flow cytometry assays.

2 Distress

The experimental method used here is classified as causing light distress. The mice will experience short-term mild pain during awakening after vaccination, and no significant damage to the well-being of the mice is expected.

3 Expected benefit

Nykode Therapeutics is a world leader in designing safe cancer vaccines that are unique to tumor type and showed promising data from two clinical trials targeting various indications. The proof-of-principle data that we generate through this pre-clinical trial in mouse models will validate our bioinformatic platform-based identification of multiple types of cancer antigens and will provide mechanistic insight into the immune system activation and tumor rejection. The pre-clinical experiments will provide an opportunity for Nykode to submit applications to conduct DNA vaccine-based immunotherapy in clinical trials, to provide the new line of treatment opportunities for cancer patients.

4 Number of animals, and what kind

In this proposed experiment, we will use 1044 mice (Mus musculus), Strain/Line: C57BL/6, BALB/c.

5 How to adhere to 3R

The in vivo experiments in mice are the only available option to evaluate the ability of vaccines to induce T cell immune responses. Our extensive expertise with this type of mice experiment as well as other published studies in the field indicates that it is appropriate with the number of animals outlined to observe significant differences between the groups in the experiment. The DNA vaccination method we have chosen to use is well-established and efficient at delivering DNA with low risk of adverse effects. Also, the animals are anesthetized with sevoflurane during vaccination to limit distress from the procedure.