System for immunotherapy targeting tumor propagation and progression
Finding biologically relevant cancer markers is key to developing an effective treatment. Once specific antigens have been identified that are present on the cell population responsible for propagating tumors, T cells can be genetically altered to target these antigens and then used for personalized T cell therapy. A method to identify and select peptide antigens that effectively associate with and are presented by host HLA surface molecules originating from tumor cells responsible for the persistence and propagation of a cancer has been developed. The system of using these data to produce T cells engineered to express T cell receptors recognizing the peptide antigens is used in the production of a personalized adoptive T cell therapy for cancer that eliminates the cells capable of tumor propagation and cancer progression. The system is especially useful in the production of cancer treatments to achieve complete durable remission of cancers of epithelial origin.
1. An isolated tumor C-RC cell population prepared by
(a) obtaining a tumor sample from an individual;
(b) cultivating the tumor sample under conditions that induce a stress response in non-C-RC differentiating and differentiated cells leading to apoptosis and necrosis but permit C-RC cells to propagate through the activation of a regenerative response;
(c) isolating the dominant actively expanding, most rapidly dividing population of cells from step (b); and
(d) culturing the cells to obtain a population of 51% to 100% C-RC,
in a serum-free, defined cell culture medium containing agents selected from the group consisting of agents inducing the apoptosis and/or necrosis of the cells, cAMP elevating agents, agents inhibiting cell-cell adhesion, nitric oxide, tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL1-α), interferon-gamma (IFN-γ), agents disrupting cell adhesion, agents interfering with survival of more differentiated cells, and calcium in a concentration of less than about 1 mM calcium,
wherein 80-100% of the C-RC population consists of actively expanding and dividing VSEC, SDEC and SCEC cells and abnormal transit amplifying cells.