Compositions and methods for CAR T cell therapy
The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.
1. A method of treating a patient for cancer, the method comprising:
i) administering to the patient an amount of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a folate linked to fluorescein isothiocyanate (FITC);
ii) administering to the patient a chimeric antigen receptor T cell (CAR T cell) composition comprising CAR T cells comprising a polypeptide having the sequence set forth in SEQ ID NO: 2; and
iii) reducing or preventing cytokine release syndrome (CRS) or cytokine storm by administering to the patient an amount of a rescue agent comprising fluoresceinamine, FITC, or fluorescein, or a salted form thereof,
wherein the amount of the rescue agent is in molar excess relative to the amount of the compound and the molar excess is less than 100-fold molar excess relative to the amount of the compound;
whereupon the patient is treated for cancer.
2. The method of claim 1 , wherein the cancer is a folate receptor-expressing cancer.
3. The method of claim 1 , wherein the CAR has a recognition region and the recognition region is a single chain fragment variable (scFv) region of an anti-FITC antibody, wherein the CAR has a co-stimulation domain and the co-stimulation domain is CD137 (4-1BB), and wherein the CAR has an activation signaling domain and the activation signaling domain is a T cell CD3ζ chain.
4. The method of claim 1 , wherein the compound, or the pharmaceutically acceptable salt thereof, is not an antibody, and does not comprise a fragment of an antibody.
5. The method of claim 1 , wherein iii) comprises administering to the patient sodium fluorescein.
6. The method of claim 5 , wherein, prior to (iii), the patient shows signs of CRS or cytokine storm, and (iii) reduces CRS or cytokine storm.
7. The method of claim 6 , which further comprises determining a CRS grade in the patient and, when the CRS grade is 1, 2, 3 or 4, administering the amount of the rescue agent.
8. The method of claim 1 , wherein, prior to (iii), the patient shows signs of CRS or cytokine storm, and (iii) reduces CRS or cytokine storm.
9. The method of claim 8 , which further comprises determining a CRS grade in the patient and, when the CRS grade is 1, 2, 3 or 4, administering the amount of the rescue agent.
10. The method of claim 1 , wherein the method results in a decrease in tumor volume in the patient.