Approach to Cancer
Developing immune medicines for patients with cancerDespite significant progress in recent years, current off-the-shelf immune medicines are only efficacious in a subset of cancer patients and expand T cells in a non-specific manner which may result in significant side effects. Autologous immune therapies that are produced for one patient are only available to treat a limited number of hematological cancers.
Repertoire is developing two distinct off-the-shelf therapeutic approaches that have the potential to treat most solid and hematological cancers and overcome the limitations of today's immunotherapies, providing hope for patients facing a cancer diagnosis.
TCR bispecific immune medicines
Our off-the-shelf T cell receptor (TCR) bispecific immune medicines comprise a TCR that binds with high affinity and precision to a tumor-specific epitope and an anti-CD3 moiety that engages and re-directs T cells to kill tumors.
We use our proprietary DECODE platform to discover TCRs from T cells that have infiltrated patient tumors by determining the specificity of the T cell to epitopes that are presented on the tumors as well as the phenotype of the T cell. TCRs are selected from cytotoxic CD8+ T cells that are clonally expanded and have an exhausted phenotype which indicates that these T cells have encountered tumor antigens, have tumor relevance, and the ability to kill tumor cells via their TCR. We then engineer these TCRs to increase their affinity, while maintaining their tumor specificity.
Our TCR bispecific immune medicines have the potential to effectively treat most solid and hematological cancers in a large proportion of cancer patients, even those with “cold” tumors and, unlike autologous medicines, can be manufactured cost effectively at scale. We are currently developing TCR bispecific therapeutics for multiple prevalent solid tumors, such as non-small cell lung cancer, triple negative breast cancer, head and neck cancer, colorectal cancer, and bladder cancer.
Our advantage
- DECODE discovers novel, tumor-specific epitopes from a target space that is 10-fold larger than competing approaches, thereby enabling our TCR bispecific immune medicines to drive effective tumor killing across all tumor types.
- DECODE discovers TCRs from patient-derived tumor infiltrating lymphocytes that are more selective and have higher epitope binding affinity than TCRs from peripheral T cells of healthy donors.
- DECODE discovers epitopes across all HLAs, ensuring patient equity and providing TCR bispecific immune medicines for all.
- Our TCR bispecific immune medicines provide scalable, off-the-shelf therapies.
mRNA cancer vaccines
We are developing off-the-shelf mRNA cancer vaccines that comprise of shared and highly immunogenic tumor-specific epitopes encoded by mRNA and encapsulated in a lipid nanoparticle for systemic delivery. The vaccines robustly activate and induce the proliferation of cytotoxic T cells that target multiple tumor-specific epitopes and therefore have the potential to be highly efficacious and overcome tumor immune evasion.
Using our DECODE platform, we are uniquely able to identify selected epitopes with precision and match them to patient HLAs. Inclusion of Class I HLA epitopes in the cancer vaccine elicits a robust cytotoxic CD8+ T cell response to kill tumors, while the addition of Class II HLA epitopes augments the anti-tumor effect by providing additional CD4+ T cell help to cytotoxic T cells.
With the ability to identify the optimal, tumor-specific epitopes for all HLAs, our mRNA vaccines have the potential to address cancers in patients across genetic backgrounds and ethnicities. We are currently developing cancer vaccines for patients with non-small cell lung cancer and colorectal cancer.
Our advantage
- DECODE uniquely discovers the most presentable, tumor-specific epitopes across Class I and Class II HLAs, thereby overcoming limitations of computational algorithms.
- DECODE determines which of the presentable Class I and Class II epitopes are most immunogenic in patients and have the potential to drive effective tumor killing.
- DECODE identifies the phenotype of T cells, enabling immune monitoring during clinical development, thereby potentially shortening the time to market.
- Our mRNA cancer vaccines provide scalable, off-the-shelf therapies for cancer.
With our DECODE platform, we have the ability to design and develop targeted immune medicines.
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