The immune system plays a critical role in protecting the body against pathogens and malignancies by locating and eliminating unwanted cells, including cancer cells. The healthy immune system employs several inherent mechanisms to balance the immune response, ensuring that unwanted cells are eliminated without harmful local tissue damage. These mechanisms include:
- Upregulations of check-point molecules, such as PD-L1/L2, that suppress the activity of effector T-cells
- Secretion of catabolic enzymes limiting the availability of amino acids required for immune cell survival, growth, and function
- Recruitment of immune regulatory cell subsets, such as regulatory T-cells and myeloid derived suppressor cells (MDSCs), via secretions of chemoattractant molecules.
Cancer cells adopt one or more of these strategies making the tumor microenvironment less conducive for anti-tumor immunity, and thus enabling the cancer cells to escape immune attack and continue to grow and metastasize.
IO Biotech is developing a new class of immune modulating therapies (T-win®) designed to engage and activate T-cells, that specifically target cells that express immune suppressive molecules such as the checkpoint molecule PD-L1, the catabolic enzymes IDO and arginase as well as the chemokine CCL22. Treatment with T-win® vaccination induces proinflammatory and cytotoxic T cell responses against cells that are contributing to immune suppression in the tumor (this includes tumor cells as well as immune cells such as tumor-associated macrophages and myeloid-derived suppressor cells), resulting in conversion of the tumor microenvironment from immune suppressive (“cold”) to a pro-inflammatory (“hot”) state.
Our unique T-win® technology platform allows us to identify, design, and validate new immune modulating vaccine candidates in humans. Our T-win® molecules are designed to engage and boost antigen-specific anti-regulatory T-cells in vivo based on a validated and safe peptide vaccination platform.
Peptide-based vaccines is a validated and safe approach to engage and stimulate T-cell in humans. The benign safety profile and flexible treatment regimen make T-win® vaccines suitable as effective single agent therapies and as combination partners with other cancer therapies, adding treatment efficacy without additional toxicity.
Immunoregulatory antigens - novel targets for cancer immunotherapy
Chinese Clinical Oncology, March 2018
The Balance Players of the Adaptive Immune System
Cancer Research, February 2018
Anti-regulatory T cells
Seminars in Immunopathology, September 2016
Novel understanding of self-reactive T cells
OncoImmunology, August 2015
Immune Regulation by Self-Recognition: Novel Possibilities for Anticancer Immunotherapy
Journal of the National Cancer Institute, June 2015