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:
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 platform is designed to enable engineered T cells to address key challenges for solid cancer treatment: target specificity and validation, broad applicability and precise non-viral genome engineering for exclusive on-tumor targeting.
Target Specificity: Personalized neoantigens in blood are not only predicted but also verified using our proprietary imPACT Isolation Technology®
Broad applicability across all solid cancers & all patient ethnicities: Patient's own tumor-specific neoTCRs guide PACT to engineer neoTCR T cells for that patient
Precision non-viral genome engineering: Produces functionally natural neoTCR T cells of a younger phenotype which are known to persist longer inside a patient after infusion
Scalable manufacturing: Proprietary TrifeCtaR™ Modular in-house GMP manufacturing
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