Treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor
The present invention relates to compositions and methods for the treatment of a canine CD20 positive disease or condition using a canine CD20-specific chimeric antigen receptor. One aspect includes a modified canine T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity in canine.
1. A method of treating a CD20+ cancer in a canine, the method comprising administering to the canine a modified cell that expresses a chimeric antigen receptor comprising a canine CD20 antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the canine CD20 antigen binding domain comprises an anti-CD20 single-chain variable fragment (scFv) comprising SEQ ID NO: 2.
2. The method of claim 1 , wherein the modified cell is selected from the group consisting of a T cell, a natural killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.
3. The method of claim 1 , wherein the modified cell is autologous to the canine.
4. The method of claim 1 , further comprising administering an antitumor vaccine to the canine.
5. The method of claim 4 , wherein the modified-canine-T cell and the antitumor vaccine are co-administered to the canine.
6. The method of claim 1 , wherein the cancer is selected from the group consisting of lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, lymph nodes cancer, bone marrow cancer, liver cancer, spleen cancer, ovarian cancer, renal cell carcinoma, bladder cancer, kidney cancer, testicular cancer, prostate cancer, breast cancer, colon cancer, pancreatic cancer, lung cancer, stomach cancer, eye cancer, skin cancer and any combination thereof.
7. The method of claim 6 , wherein the cancer is Hodgkin's lymphoma or non-Hodgkin's lymphoma.
8. The method of claim 1 , wherein the costimulatory signaling region comprises an intracellular domain of a costimulatory molecule selected from the group consisting of CD8, CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof.