Universal immune cells for cancer immunotherapy
Embodiments of the disclosure encompass adoptive immunotherapy related to cells expressing multiple chimeric antigen receptors (CARs). In specific embodiments, T cells express a HER2-specific CAR, an IL13 Rα2-specific CAR, and an EphA2-specific CAR. In particular embodiments, the cells are utilized for cancer treatment, including for glioblastoma.
1. A method of treating glioma in an individual, comprising the step of delivering to the individual a therapeutically effective amount of cells comprising:
a) an expression construct that encodes a HER2-specific chimeric antigen receptor (CAR);
b) an expression construct that encodes an IL13Rα2-specific CAR; and
c) an expression construct that encodes an EphA2-specific CAR,
wherein the expression constructs of a), b), and c) are located on the same molecule, wherein the cells express the HER2-specific CAR, the IL13Rα2-specific CAR, and the EphA2-specific CAR.
2. The method of claim 1 , wherein the individual has a cancer that expresses HER2, IL13Rα2, and EphA2.
3. The method of claim 1 , comprising the step of analyzing a sample comprising cancer cells from the individual for one or more antigens on one or more cancer cells.
4. The method of claim 3 , wherein the cells comprising the composition are produced to target one or more particular antigens based on an outcome of the analyzing step.
5. The method of claim 1 , wherein the expression constructs of a), b), and c) are a total of at least 4.6 kb in size.
6. The method of claim 1 , wherein the expression constructs of a), b), and c) do not comprise any identical sequences greater than 50 bp in length.
7. The method of claim 1 , wherein the individual was previously treated for glioma with a previous treatment.
8. The method of claim 7 , wherein the individual was refractory for the previous treatment.
9. The method of claim 1 , wherein the cells further comprise an expression construct that encodes an additional CAR that targets a tumor antigen that is not HER2, IL13Rα2, or EphA2, wherein the cells express the additional CAR.