Presenting cell and use thereof in cell therapy
The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion and/or maintenance in vivo and/or in vitro. For example, in a method of in vivo cell expansion, the method comprises administering an effective amount of cells comprising an antigen binding molecule to a subject; and administering an effective amount of presenting cells expressing a solid tumor antigen that the binding molecule binds.
1 . A method of expanding lymphocytes or enhancing expansion of lymphocytes, the method comprising:
administering an effective amount of lymphocytes to a subject having a solid tumor;
administering an effective amount of an agent to the subject, wherein the agent stimulates or activates antigen presenting cells (APCs) of the subject, and wherein the agent comprises a chimeric antigen receptor (CAR) T cell binding a B cell, a bispecific antibody binding a B cell and a T cell, an antibody binding a B cell, or a combination thereof; and
allowing the lymphocytes to expand in the subject.
2 . The method of claim 1 , wherein the APCs comprise dendritic cells, macrophages, Langerhans cells, B cells, T cells, or a combination thereof.
3 . The method of claim 1 , wherein the APCs comprise B cells.
4 . The method of claim 1 , wherein the agent stimulates or activates B cells to differentiate into plasma cells.
5 . The method of claim 1 , wherein the agent comprises an antibody binding a B cell.
6 . The method of claim 1 , wherein the agent comprises a single-chain variable fragment (scFv) binding a B cell.
7 . The method of claim 1 , wherein the lymphocytes comprise T cells or NK cells, or a combination thereof.
8 . The method of claim 1 , wherein the agent binds a B cell antigen.
9 . The method of claim 8 , wherein the B cell antigen comprises CD19, CD20, CD22, CD53, CD138, BCMA, CD38, FCRL5, or a combination thereof.
10 . The method of claim 1 , wherein the APCs comprise B cells, and the agent stimulates or activates the B cells to up-regulate CD40, CD80, CD86, or a combination thereof on the B cells.
11 . The method of claim 1 , wherein the APCs comprise B cells, and the agent stimulates or activates B cells to up-regulate CCL17 and CCL22.
12 . The method of claim 1 , wherein the APCs comprise B cells, and wherein the agent stimulates or activates the B cells such that at least a portion of the B cells differentiate into plasma cells or into cells having one or more phenotypes of a plasma cell.
13 . The method of claim 1 , wherein the lymphocytes comprise a CAR or T cell receptor (TCR).
14 . The method of claim 13 , wherein the CAR comprises an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain.
15 . The method of claim 14 , wherein the antigen-binding domain binds a tumor antigen comprising MUC1 (tMUC1), PRLR, CLCA1, MUC12, GUCY2C, GPR35, CR1L, MUC 17, TMPRSS11B, MUC21, TMPRSS11E, CD207, SLC30A8, CFC1, SLC12A3, SSTR1, GPR27, FZD10, TSHR, SIGLEC15, SLC6A3, CLDN 18.2, KISS1R, QRFPR, GPR119, CLDN6, UPK2, ADAM12, SLC45A3, ACPP, MUC21, MUC16, MS4A12, ALPP, CEA, EphA2, FAP, GPC3, IL13-Ra2, Mesothelin, PSMA, ROR1, VEGFR-II, GD2, FR-α, ErbB2, EpCAM, EGFRvIII, MAGE A4, EGFR, or a combination thereof.
16 . The method claim 14 , wherein the CAR comprises an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain, and wherein the intracellular signaling domain comprises a signaling domain, or a signaling domain and a co-stimulatory signaling domain, and wherein the signaling domain and co-stimulatory signaling domain comprise a functional signaling domain of a protein comprising CD27, CD28, 4-1BB (CD137), 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, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD160, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, NKp44, NKp30, NKp46, NKG2D, or a combination thereof.
17 . The method of claim 13 , wherein the TCR is a modified TCR, the TCR is derived from spontaneously occurring tumor-specific T cells in a patient, and/or the TCR binds a tumor antigen.
18 . The method of claim 17 , wherein the tumor antigen comprises CEA, gp100, MART-1, p53, MAGE-A3, NY-ESO-1, or a combination thereof.
19 . A method of expanding T cells or enhancing expansion of T cells, the method comprising:
administering an effective amount of T cells to a subject having solid tumor;
administering an effective amount of an agent to the subject, wherein the agent stimulates or activates B cells of the subject, and wherein the agent comprises a CAR T cell binding a B cell, a bispecific antibody binding a B cell and a T cell, an antibody binding a B cell, or a combination thereof; and
allowing the T cells to expand in the subject.
20 . The method of claim 19 , wherein the agent stimulates or activates the B cells to differentiate into plasma cells or to up-regulate CCL17 and CCL22.
21 . The method of claim 19 , wherein the agent comprises an antibody binding a B cell.