Modified cell expansion and uses thereof

• US 10,561,686 B2
• Filed: 09/28/2018
• Issued: 02/18/2020
• Est. Priority Date: 01/12/2018
• Status: Expired due to Fees

• Current Assignee: Innovative Cellular Therapeutics Holdings, Ltd.
• Original Assignee: Innovative Cellular Therapeutics Co., Ltd.
• Inventors: Xiao, Lei, Pu, Chengfei, Cao, Zhiyuan, Wu, Zhao
• Primary Examiner(s): Bristol, Lynn A
• Application Number:
  US16/146,218
• Publication Number:
  US 20190216851A1
• Time in Patent Office: 508 Days
• Field of Search: 4241331, 424 9321
• CPC Class Codes: A61K 2239/29 Multispecific CARs
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61K 39/46447 Mucins, e.g. MUC-1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/3092 against tumour-associated mucins
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/75 containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Abstract

The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion in vivo and/or in vitro. For example, a cell may comprise a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR may recognize a surface molecule of a blood cell.

Claims

1. A method for enhancing T cell expansion in a subject having cancer, the method comprising:

obtaining modified T cells comprising a chimeric antigen receptor (CAR) binding tMUC comprising an amino acid sequence of SEQ ID NO;

70 and a CAR binding CD19 comprising an amino acid sequence of SEQ ID NO;

5 or 6, wherein the CAR comprises an antigen binding domain, a transmembrane domain, and a cytoplasmic domain and wherein the modified T cells comprise autologous T cells derived from the subject; and

administering an effective amount of the modified T cells to the subject, wherein the modified T cells enhance the expansion of the modified T cells in the subject as compared to the subject administered with modified T cells comprising the CAR binding CD19 in the absence of CAR binding tMUC or administered with modified T cells comprising the CAR binding tMUC in the absence of CAR binding CD19.

2. The method of claim 1, wherein the cytoplasmic domain comprises a co-stimulatory domain, CD3 zeta domain, or a combination thereof.

3. The method of claim 1, wherein the T cell expansion is greater than a T cell expansion obtained by administering modified T cells comprising the CAR binding tMUC in the absence of the CAR binding CD19.

4. The method of claim 3, wherein the T cell expansion is measured based on an increase in copy number of CAR molecules in genomic DNA of the modified T cells in peripheral blood of the subject having cancer.

5. The method of claim 1, wherein the CAR binding CD19 comprises an amino acid sequence of SEQ ID NO:

203, 207, 216, or 219.

6. The method of claim 1, wherein the CAR binding tMUC comprises an amino acid sequence of SEQ ID NO:

202 or 205.

7. The method of claim 1, wherein the modified T cells comprise a nucleic acid sequence of SEQ ID NO:

201, 204, 206, 208, 215, 217, 218, or 220.

8. The method of claim 1, wherein the enhancing T cell expansion in the subject having cancer comprises enhancing expansion of the modified T cells in peripheral blood of the subject having cancer.

9. The method of claim 1, wherein the cancer is breast cancer.