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 tumor cells called “neoantigens.” Selected peptides that are both derived from neoantigens binding to the patient’s HLA and recognized by autologous T cells are called neoepitopes (neoE). These neoEs are designed to be highly specific to each person’s cancer with less than one percent of these peptide-HLA targets shared among individuals with solid cancer. T cells capable of targeting neoepitopes from tumor-specific mutations hold the potential to recognize and kill tumor cells.
PACT has developed a high-throughput technology called imPACT Isolation Technology®. This technology allows us to identify and capture neoE-specific T cells from peripheral blood. Following manufacturing of these specific T cells, the PACT platform directs a patient’s own immune system to trigger a response directly against their specific tumor mutations:
- Our proprietary functional verification and characterization process allows us to choose the T cells for potential 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 Personalized Therapy for Every Patient
Tumor immunogenicity is not only patient specific but inherently exclusive to the individual tumor itself. Tumor-specific mutations are presented to T cells on Human Leukocyte Antigens (HLA) molecules. These neo-epitope-HLA protein targets are different for each cancer patient. Less than 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 snares for each patient regardless of ethnicity. These neoE-HLA snares 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 neoE-HLA tumor targets.
Following imPACT Isolation Technology®, our bioinformatics algorithms define the most therapeutically relevant neoantigens present in each patient's tumor, from which we extract the T cell receptor (TCR) sequences for PACT product development. Using non-viral precision genome engineering, the neoTCR replaces 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 Approach to Developing Personalized T-Cell Therapies
Predict and prioritize targets from tumor mutation sequencing
PACT receives patient tumor biopsy and peripheral blood samples
PACT deep sequences patient tumor biopsy specimen to derive sequence information
PACT’s proprietary bioinformatic algorithms effectively predict and prioritize a list of potential neoE-HLA targets that are most likely to mount an immune response