Glypican 3 specific T cell receptors for adoptive T cell therapy
Cáncer
Target:
GPC3 (Glypican 3)
- Introduction:
Identification of different TCR clonotypes specific for an HLA-A2-restricted epitope of GPC3. Cloning and application of these TCRs in the treatment of hepatocarcinoma.
- Results:
The developed TCRs recognize and eliminate HLA-A2+GPC3+ tumor cells and have great potential for engineering the patient's autologous T cells to treat GPC3+ tumors.
- Keywords:
- Cáncer ,
- Terapia celular ,
- Hepatocarcinoma
- Early Discovery
- Discovery
- Preclinical
- Clinical
- Diagnostics
Approach
- Our laboratory has identified different TCR clonotypes specific for an HLA-A2-restricted epitope of GPC3.
- TCRs have been cloned and primary human T cells have been genetically modified with amphotropic retrovirus coding for these TCRs.
- We have analyzed the capacity of GPC3-TCR redirected T cells to recognize and kill HEPG2 hepatoblastoma tumor cells (naturally HLA-A2+GPC3+).
- These data support the hypothesis that the loss of PLA2G4E might play a key role in AD onset and/or progression.
Key concepts and Target Identification
- Primary human T cells expressing GPC3 TCRs specifically recognize HEPG2 tumor cells, exhibiting intense upregulation of the activation-dependent molecule CD137. They also proliferate and produce effector cytokines.
- Importantly, human T cells expressing GPC3 TCRs specifically kill HEPG2 tumor cells in a major histocompatibility complex (MHC) class I-dependent manner.
- Certain preferred TCRs, such as TCR-6, demonstrate excellent effector functions against HEPG2 tumor cells.
Target Validation
- In vitro experiments demonstrated that human T cells genetically engineered to express GPC3-specific TCRs are able to recognize and kill HLA-A2+GPC3+ tumor cells.
- These TCRs have a great potential to engineer patient's autologous T cells to treat GPC3+ tumors.
Intellectual Property
New Patent application to be filed.