Approach
Each person’s cancer is driven by a unique set of mutations that can code for cancer-specific proteins that are displayed on the cancer cell’s surface. Thus, they represent a new class of patient-specific cancer targets called “neoantigens.” Each neoantigen contains “neoepitopes” (neoE), which are the portion of the neoantigen that are displayed on the cell surface. These neoepitopes are specifically recognized by T cells within the patient’s own immune response. T cells capable of targeting neoepitopes from tumor-specific mutations hold the potential to recognize and kill tumor cells.
PACT has developed an ultra-sensitive, high-throughput technology called imPACT Isolation Technology®. This technology allows us to identify and capture these rare neoE-specific CD8+ T cells from peripheral blood. Following manufacturing of these specific T cells, the PACT platform directs a person’s own immune system to trigger a response directly against their specific tumor mutations:
- Our proprietary functional characterization process allows us to choose the most relevant, antigen experienced, CD8+ T cells for therapeutic benefit to the patient, from which we extract the T cell receptor (TCR) sequences to develop a polyclonal product.
- Using non-viral precision genome engineering, the neoE-targeted TCR sequences replace the endogenous TCR of fresh CD8 and CD4 T cells collected by apheresis from that same patient’s peripheral blood (autologous neoE TCR engineered into autologous fresh T cells).
- The engineered cells are expanded in culture and subsequently reinfused into the patient.
A Unique Therapy for Every Patient
It is now broadly accepted that cancer is a profoundly patient-specific disease, where no two tumors are alike. Tumor immunogenicity is not only patient specific but inherently exclusive to the individual tumor itself. Tumor-specific mutations are presented to CD8+ T cells on Human Leukocyte Antigens (HLA) molecules. These neo-epitope-HLA protein targets are different for each cancer patient. Only <0.001% - 1% of neo-epitope specific HLA (neoE-HLA) targets are the same among individuals with solid cancer.
PACT’s technology platform enables us to build a designer library of neoE-HLA protein targets for each patient regardless of ethnicity. These soluble neoE-HLA proteins are then assembled into barcoded “snare libraries” for the interrogation of matched peripheral blood mononuclear cells (PBMCs) from that patient for CD8 T cells that specifically bind the cognate neoE-HLA tumor targets.
Following imPACT Isolation Technology®, our machine learning algorithms define the most relevant neoE specific CD8 T cells for therapeutic benefit, from which we extract the T cell receptor (TCR) sequences for PACT TCR product development. Using non-viral precision genome engineering, the neoE-targeted TCR sequences replace the endogenous TCR of fresh CD8 and CD4 T cells collected from that same patient’s peripheral blood by leukapheresis (autologous neoE TCR engineered into autologous fresh T cells) for re-infusion into the patient.
Our End-to-End Cell Therapy Process
Predict tumor-specific display of patient neo-antigens
PACT receives patient tumor biopsy and PBMC samples
PACT conducts DNA/RNA sequencing of the tumor biopsy and DNA sequencing of PBMC
PACT’s proprietary bioinformatic algorithms effectively predict tumor-displayed & truncal neoE-HLA targets
Publications
Explore published research on personalized T-Cells for cancer from PACT scientists.