Ref.: DS Chen, I Mellman. Immunity 2013;12:1-10
We have been committed to the field of cancer immunotherapy for more than a decade, and are exploring a broad range of innovative therapeutic agents that harness the cancer immunity.
Transformed cells express some tumor-specific proteins and also accumulate somatic mutations during proliferation and progression. The antigens derived from the tumor-specific proteins (TSAs) as well as antigens containing somatic mutations (neoantigens) are inherently non-self; thus, they exactly appear foreign to the immune system. Currently, the neoantigens presented on cell surface are believed to be a significant marker for the recognition of transformed neoplastic cells by the immune system.
As cancer cells accumulate the mutations, they are genetically unstable and evade immune attack by altering gene expression and function. For example, cancer cells often stop displaying neoantigens on the cell surface and initiate to express immune checkpoint proteins such as PD-L1 to block cancer immunity, causing immune-resistance and immunosuppression. Therefore, removing immune-suppression as well as inducing cancer immunity improve the patient’s immune response and provide greater therapeutic benefits.
The immune-resistant or immunosuppressive tumors are pathologically heterogeneous among patients according to the number of genetic mutations, the state of the immune system and the tumor micoroenvironmental conditions. These strongly affect the efficacy of cancer immunotherapy, and limit the therapeutic benefits to only a subset of cancer patients. Thus, we believe that profiling patients, developing immune-monitoring methods and designing patient-specific combination therapies are essential for successful cancer immunotherapy (personalized medicine). We also believe that approaches targeting multiple steps in the cancer immune cycle will enhance cancer immunity by redirecting it to fight cancer (integrated medicine).
In line with this, we are developing cancer immunotherapies according to the following themes.
|Cancer-immunity challenges to overcome||Approach||Our pipeline|
|Insufficient T cell activation and infiltration||Insufficient antigen||Customization of antigens for maximum immune responses in individual patients||Exploratory||Neoantigen vaccine|
|Increased antigen release after cancer cell death||Exploratory||Immunogenic cell death induction|
|Dendritic cell dysfunction||Enhancement of antigen-presenting function||Exploratory||Related to dendritic cells|
|T cell dysfunction||Increased NKT cell with high cancer immunity through infusion||iPS-NKT||iPS-NKT-derived regenerated NKT cell therapy|
|Infusion of cancer-specific T cell with enhanced function||BP2301||HER2 CAR-T|
|Immunosuppression at tumor site||Combination with immune modulation||GRN-1201||Peptide vaccine in combination with immune checkpoint blockade|
|Multiple immune checkpoint blockade||Exploratory||Blocking antibody for non-PD pathway blockade|