Philadelphia-based biopharmaceutical company Adaptimmune Therapeutics (NASDAQ: ADAP) has announced the presentation of data supporting the cancer-fighting activity of their “off-the-shelf” iT SPEAR T cell platform at the annual meeting of the American Society for Gene and Cell Therapy (ASGCT).
The poster, titled “Driving ADP-A2M4 SPEAR Expression from an Endogenous Hematopoietic Lineage Promotor for “Off-the-Shelf” T-Cell Therapy for MAGE-A4+ Solid Tumors,” demonstrated that their engineered iT cells expressing the ADP-A2M4 T cell receptor (TCR), derived from genetically modified human induced pluripotent stem cells (hiPSCs), could eliminate target cancer cells in vitro.
The data suggest that the SPEAR iT cell technology has the “potential to be an efficacious cell therapy,” Adaptimmune stated in their press release.
Adaptimmune’s SVP of Allogeneic Research Jo Brewer, PhD, stated, “We have clearly demonstrated that we can make T-cells from stem cells. These cells express our engineered SPEAR TCR targeting MAGE-A4 and can kill tumor cells in vitro as effectively as control cells. We have also reached a milestone in editing our engineered TCRs into the hiPSC genome to enable successful differentiation.”
“This is one critical element as we plan to build large banks of pluripotent cells for our proprietary differentiation process, to generate functional T-cells expressing our engineered receptors. These are great advances as we prepare for clinical use,” Dr. Brewer continued.
Specific peptide enhanced affinity receptor (SPEAR) T cells are engineered to enable the specific targeting and destruction of solid tumors, a type of cancer that has proven resistant to treatment with chimeric antigen receptor (CAR) T cell technology.
The T-cell receptor (TCR) genes of SPEAR T cells have been modified at elements encoding the complementarity determining regions (CDRs) of the variable chains, which are important for mediating the interaction between the TCR and HLA-peptide complex of target cancer cells that leads to protective T cell responses. SPEAR T cells are intended to recognize cancer cells with greater specificity to minimize cross-reactivity with healthy human cells.
SPEAR T cells are currently being evaluated clinically for the treatment of solid tumors expressing the cancer antigens MAGE-A10, MAGE-A4, or AFP, proteins frequently expressed by a high percentage of solid tumor types including lung, skin, liver, and urothelial cancers, among others.
A number of companies are developing engineered lymphocyte technologies for the treatment of solid tumors. Immunotherapy company NantKwest is planning a phase 2 trial of its Natural Killer (NK) cell-based therapy for metastatic pancreatic cancer.