JPWO2020185917A5 - - Google Patents

Claims (15)

an unconjugated targeting moiety for use with a therapeutic to treat, alleviate or inhibit cancer in a subject, comprising:
The therapeutic method comprises (i) a composition comprising a lipid bound to a targeting moiety and (ii) a cell comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) bound to the lipid. said targeting moiety may be biotin, digoxigenin, dinitrophenol, or fluorescein, said CAR or TCR can specifically bind to said targeting moiety bound to a lipid or said unbound targeting moiety, and ,
The unbound targeting moiety is not lipid bound and may be a salt of the lipid bound targeting moiety biotin, digoxigenin, dinitrophenol or fluorescein, sodium salt, disodium salt or An unbound targeting moiety characterized in that it may be a potassium salt. an unconjugated targeting moiety for use with a therapeutic in a method of treating, alleviating or inhibiting cancer in a subject, comprising:
said method comprising: (a) administering said therapeutic to said subject; and (b) administering to said subject a targeting moiety that is not lipid bound;
The therapeutic method comprises (i) a composition comprising a lipid bound to a targeting moiety and (ii) a cell comprising a chimeric antigen receptor (CAR) or a T cell receptor (TCR) bound to the lipid. said targeting moiety may be biotin, digoxigenin, dinitrophenol, or fluorescein, said CAR or TCR can specifically bind said targeting moiety bound to a lipid or said unbound targeting moiety, and The unbound targeting moiety is a salt of biotin, digoxigenin, dinitrophenol, or fluorescein, which may be the sodium, disodium, or potassium salt. 3. The unbound targeting moiety of claim 1 or 2, wherein said unbound targeting moiety is used to be administered to said subject after administration of said therapeutic regimen. The effector function of the CAR- or TCR-comprising cell upon administration of the unbound targeting moiety is lower than the effector function of the CAR- or TCR-comprising cell in the absence of the unbound targeting moiety. and/or
Cytokine production from cells comprising said CAR or TCR upon administration of said unbound targeting moiety is equivalent to production of cytokines from cells comprising said CAR or TCR in the absence of said unbound targeting moiety. An unbound targeting moiety according to any one of claims 1 to 3 which is less than . An unbound targeting moiety according to any one of claims 1 to 4, wherein said targeting moiety bound to a lipid comprises biotin, digoxigenin, dinitrophenol, fluorescein or derivatives thereof. An unbound targeting moiety according to any one of claims 1 to 5, wherein said targeting moiety bound to a lipid comprises fluorescein or a derivative thereof. wherein said unbound targeting moiety is a salt selected from salts of biotin, salts of digoxigenin, salts of dinitrophenol and salts of fluorescein , and may be sodium, disodium or potassium salts; 7. An unbound targeting moiety according to any one of clauses 1-6 . An unbound targeting moiety according to any one of claims 1 to 7, wherein said unbound targeting moiety is a salt of fluorescein, which may be the sodium or disodium salt. 9. Any one of claims 1-8 , wherein said targeting moiety bound to a lipid is fluorescein and said unconjugated targeting moiety is a salt of fluorescein, which may be a sodium or disodium salt. 3. An unbound targeting moiety as described in . The unbound targeting moiety of any one of claims 1-9 , wherein said lipid comprises an ether phospholipid (PLE). hematopoietic stem cells ; CD8+ cytotoxic T lymphocytes selected from the group consisting of naive CD8+ T cells, central memory CD8+ T cells, effector memory CD8+ T cells and bulk CD8+ T cells. or CD4+ helper T lymphocytes selected from the group consisting of naive CD4+ T cells, central memory CD4+ T cells, effector memory CD4+ T cells and bulk CD4+ T cells . or an unbound targeting moiety according to claim 1. The cancer is colon cancer, breast cancer, ovarian cancer, lung cancer, pancreatic cancer, prostate cancer, malignant melanoma, kidney cancer, brain tumor , glioblastoma, neuroblastoma, medulloblastoma, sarcoma, An unbound targeting moiety according to any one of claims 1 to 11, which is a solid tumor such as bone cancer, liver cancer; or a non-solid tumor such as leukemia, multiple myeloma. The unbound targeting moiety of any one of claims 1-12 , wherein the subject is a mammal, which may be a human . The unbound targeting moiety of any one of claims 1-13, wherein said CAR or TCR is capable of specifically binding fluorescein. The unbound targeting moiety of any one of claims 1-14 , wherein said CAR or TCR comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-6.