PICI’s research efforts will span the entire field of cancer immunology:
PICI will additionally make large bets on three major cross-cutting collaborative research projects – to develop best-in-class T-Cells, discover novel pathways and new treatments to improve checkpoint blockade responses, and identify new tumor-specific markers for immune recognition.
In the best-known forms of cell-based therapy, known as CAR-T (Chimeric Antigen Receptor T-Cell) or TCR (T-Cell Receptor) therapy, the immune system’s main anti-cancer warriors, T cells, are harvested from a patient’s blood and genetically engineered to target proteins or peptides that are abundant in the patient’s tumor. This population of modified cells is expanded by 1000-fold or more and returned to the patient’s bloodstream, where the cells seek out and attack tumors. Parker Institute scientist Carl June, MD, has pioneered CAR-T therapy for acute lymphoid leukemia (ALL), and the therapy has been enormously successful: over 90 percent of ALL patients receiving CAR-T therapy achieved complete remission.
In order to broaden and increase the utility of T-Cell Therapy, next generation cells must by designed to be safer, survive, and remain active longer.
The team will develop laboratory and clinical studies to discovery the pathways and factors that modulate T-Cell activity and survival, and then develop a new generation of more effective T-Cell therapies.
It was once believed that the immune system may fail to eradicate cancer because of a weak immune response, or inadequate recognition of the “foreignness” of tumor cells. Accordingly, early immunotherapies were aimed at boosting the immune response. But in the 1990s, Parker Institute scientists Jim Allison, PhD and Jeff Bluestone, PhD, independently discovered that, to prevent autoimmunity and overreactions, a molecule called CTLA-4 acts as a “brake,” or checkpoint, on the immune response. This insight led to the development of drugs called “checkpoint inhibitors.” First-generation drugs that target CTLA-4 and another checkpoint molecule called PD-1 have achieved unprecedented responses in melanoma, lung and kidney cancers, and are being developed for virtually every other type of tumor.
Despite the tremendous success of checkpoint blockade agents such as anti-PD1 and anti-CTLA-4, many patients still do not respond, for reasons that are not yet fully understood.
The team will compare responders and non-responders to discover novel pathways and synergistic combination treatments that will improve response rates and broaden the utility of these agents to more types of cancer.
Since the advent of checkpoint inhibitors, scientists have revived the development of immune-boosting drugs, which include vaccines, therapeutic viruses, and substances designed to stimulate the immune system to recognize and more potently attack a patient’s tumors. The identification of new tumor-specific markers for immune recognition could improve the effectiveness and broaden the applicability of vaccines and cellular therapies to many additional types of cancer.
The identification of new tumor-specific markers for immune recognition stands to improve the effectiveness and broaden the applicability of vaccines and cellular therapies to many additional types of cancer.
The team will utilize advanced DNA sequencing, antigenic peptide discovery efforts and immune monitoring technologies to identify self and mutated proteins as novel antigens for tumor targeting, and then develop novel vaccines and CAR/TCR therapies against these targets.