Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool
Provided are a system and methods for selectively inducing expansion of a population of T cells in the absence of exogenous growth factors, such as lymphokines, and accessory cells for research purposes. The cell based expansion system and methods permit the long-term growth of CTLs, preferably human CTLs. In addition, T cell proliferation can be induced without the need for antigen, thus providing an expanded T cell population that is polyclonal with respect to antigen reactivity. Further provided are methods for using the system and methods to screen and identify antigens related to specific diseases or conditions, tumors, autoimmune disorders, or an infectious disease or pathogen, and to identify target molecule for research purposes, or for developing a vaccine based thereon.
1. A cell-based system for inducing a population of T cells to proliferate to exponential numbers, the system comprising an artificial antigen-presenting cell (aAPC) comprising a population of K562 cells engineered to express CD32 and 4-1BBL, wherein the K562 cells are further coated with anti-CD3 antibodies and anti-CD28 antibodies, wherein the system allows the population of T cells to be exposed to the aAPC,
thereby inducing the population of T cells to exponentially proliferate.
2. A cell-based system for inducing a population of CD8 + T cells to proliferate to exponential numbers, the system comprising an artificial antigen-presenting cell (aAPC) comprising a population of K562 cells engineered to express CD32 and 4-1BBL, wherein the K562 cells are further coated with anti-CD3 antibodies and anti-CD28 antibodies, wherein the system allows the population of T cells to be exposed to the aAPC,
thereby inducing the population of T cells to exponentially proliferate.