Programming a Multi-Faceted Attack on Cancer
While today’s cell-based approaches for cancer have demonstrated early promise, the vast majority share a number of features that limit therapeutic potential and/or commercial viability. In general, these approaches utilize T cells as opposed to other cytotoxic immune cells such as NK cells, involve resource-intensive manufacturing of autologous-based products, and are limited to singular targeting mechanisms. We are pioneering the development of programmed cellular immunotherapies for cancer that build upon insights gained from these first-generation cell-based approaches. We seek to develop NK and T cell cancer immunotherapies with multi-faceted therapeutic properties, functionality and scalability that are not inherently limited by the use of a patients’ own cells.
Adaptive NK Cell
Harnessing the Emergence of a Persistent & Potent NK Cell
Recent breakthroughs in cell-based cancer immunotherapy have been based on the use of T cells. NK cells, like T cells, have significant anti-tumor activity. Additionally, NK cells offer several unique advantages for use in cancer immunotherapy: the anti-tumor activity of NK cells is independent of tumor antigen exposure; the inhibitory mechanisms of NK cells prevent the killing of normal cells and tissue; and the cooperative nature between NK cells and monoclonal antibodies enables highly-targeted killing. To date, the isolation and administration of a homogenous population of persistent and potent NK cells has been challenging.
Our collaborators at the University of Minnesota have identified a distinct class of NK cells, referred to as the “adaptive” phenotype, expressing a unique metabolic program that promotes long-term persistence in vivo and has an epigenetic profile similar to that of cytotoxic T lymphocytes. Additionally, these “adaptive” NK cells can be programmed to express high levels of CD16, a cell-surface protein which allows NK cells to bind to and synergize with monoclonal antibodies for the destruction of cancer cells. In collaboration with Dr. Jeffrey Miller, M.D. at the University of Minnesota, Fate is currently advancing our programmed adaptive NK cell cancer immunotherapy through clinical translation for the treatment of solid tumors.
Pluripotent Cell‑derived Cancer Immunotherapies
A Disruptive Approach to Off-the-Shelf Engineered NK and T cell Cancer Immunotherapy
We have also established a leadership position in generating induced pluripotent cells, which are capable of long-term self-renewal and can be used to generate almost any functional cell. Two of our scientific founders, Drs. Rudolf Jaenisch and Sheng Ding are pioneers in the field, and we have built a patent-protected, robust platform that allows for the generation and maintenance of pluripotent cells in a consistent, scalable and efficient manner.
We believe that our pluripotent cell platform, which combines genetic engineering with rapid and efficient generation of immune cells, is disruptive and holds unique potential for the development of off-the-shelf NK and T cell cancer immunotherapies. Specifically, the platform is designed to enable the generation of highly-stable, genetically-modified, clonal pluripotent cell lines, and to utilize these lines for the unlimited production of engineered T cells and NK cells without requiring patient-sourced cells. We believe our therapeutic strategy is disruptive, has the potential to overcome key limitations of patient-sourced approaches, such as the requirement to isolate and engineer cells for each individual patient, and may prove to be the cornerstone of off-the-shelf cancer immunotherapy.
Engineered CAR & TCR T‑Cell Immunotherapies
Adding Therapeutic Dimensionality to Engineered T Cells
Remarkable therapeutic outcomes have been observed using T cells engineered with chimeric antigen receptors (CAR) in patients with certain blood-borne cancers. While engineered receptors have significantly enhanced the killing potential of T cells, cancer cells have proven to be resilient in their ability to evade immune cells. Through our collaboration with Juno Therapeutics, we seek to identify small molecules that can add further therapeutic dimensionality to engineered T cells. By using small molecules to program additional T cell functionality, such as T cell persistence and homing, we believe the therapeutic potential of engineered T cells may be fully-realized.