Compositions and methods for treating cancer with anti-CD19/CD22 immunotherapy
Chimeric antigen receptors containing CD19/CD22 or CD22/CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.
1. An isolated nucleic acid molecule encoding a CD19/CD22 tandem chimeric antigen receptor (CAR) comprising at least one extracellular antigen binding domain comprising a CD19/CD22 antigen binding domain, at least one transmembrane domain, and at least one intracellular signaling domain, wherein the CD19/CD22 tandem chimeric antigen receptor (CAR) is encoded by a nucleotide sequence comprising SEQ ID NO: 1, 3, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, or 82.
2. The isolated nucleic acid molecule of claim 1 , wherein the CAR is encoded by a nucleotide sequence consisting of SEQ ID NO: 1, 3, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, or 82.
3. The isolated nucleic acid molecule of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 2, 4, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, or 83.
4. A chimeric antigen receptor (CAR) encoded by the isolated nucleic acid molecule of claim 1 .
5. A vector comprising a nucleic acid molecule of claim 1 .
6. The vector of claim 5 , wherein the vector is selected from the group consisting of a plasmid vector, a cosmid vector, a herpes virus vector, a measles virus vector, a lentivirus vector, an adenoviral vector, or a retrovirus vector, or a combination thereof.
7. An isolated cell comprising the vector of claim 5 .
8. A method of making a cell comprising transducing a T cell with a vector of claim 5 .
9. The vector of claim 5 , wherein the vector is selected from the group consisting of a DNA vector or an RNA vector.
10. A pharmaceutical composition comprising an anti-tumor effective amount of a population of human T cells, wherein the population of human T cells comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR is encoded by a nucleotide sequence comprising SEQ ID NO: 1, 3, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, or 82, and wherein the T cells are T cells of a human having a cancer.
11. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising an anti-tumor effective amount of a population of T cells, wherein the population of T cells comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR is encoded by a nucleotide sequence comprising SEQ ID NO: 1, 3, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, or 82.
12. The method of claim 11 , wherein the cancer is a hematological cancer.
13. The method of claim 12 , wherein the hematological cancer is leukemia, lymphoma, or multiple myeloma.
14. The method of claim 13 , wherein the leukemia is chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), or chronic myelogenous leukemia (CML).
15. The method of claim 13 , wherein the lymphoma is mantle cell lymphoma, non-Hodgkin's lymphoma or Hodgkin's lymphoma.
16. The method of claim 11 , wherein the cancer is an oral and pharynx cancer, a digestive system cancer, a respiratory system cancer, a bone and joint cancer, a soft tissue cancer, a skin cancer, a pediatric cancer, a cancer of the central nervous system, a cancer of the breast, a cancer of the genital system, a cancer of the urinary system, a cancer of the eye and orbit, a cancer of the endocrine system, a cancer of the brain, or a combination thereof.