Patent application EP16382147A (EP), filed 2016-04-05
Publication number: EP3228701A1
Title: METHOD FOR PREPARING LYMPHOCYTES CAPABLE OF INFILTRATING A SOLID TUMOR, LYMPHOCYTES OBTAINABLE BY SAID METHOD AND USES THEREOF
Abstract: The invention relates to an  ex vivo  method for preparing lymphocytes capable of infiltrating a solid tumor in a human subject, comprising: (a) administering CD45+ cells from said subject to an immunodeficient non-human organism, wherein the non-human organism contains a xenograft of the solid tumor generated by implanting cells or tissue from the tumor into the non-human organism; (b) maintaining the non-human organism for sufficient time for the CD45+ cells to infiltrate the tumor xenograft; and (c) recovering lymphocytes from the xenograft. The invention further relates to a cellular population of lymphocytes obtainable by said method and uses thereof.
IPC codes: A61K  35/    17            A I
A61K  49/    00            A I
C12N   5/  0783            A I
Claims: number: 1
text: A method for theex vivo preparation of lymphocytes capable of infiltrating a solid tumor in a human subject, comprising:
number: 2
text: The method of claim 1, wherein the solid tumor is selected from the group consisting of lung, genitourinary, gynecologic, breast, head and neck, central nervous system, kidney, pancreatic, and any other gastrointestinal tumor.
number: 3
text: The method of any of claims 1 or 2, wherein the immunodeficient non-human organism lacks T and B lymphocytes and Natural Killer (NK) cells.
number: 4
text: The method of any of claims 1 to 3, wherein the immunodeficient non-human organism is a NOD/SCID/IL2λ receptor null (NSG) mouse.
number: 5
text: The method of any of claims 1 to 4 wherein the xenograft is implanted in the non-human organism in the vicinity of the organ in which the tumor is found in the human subject, in of the organ in which the tumor is found in the human subject or subcutaneously.
number: 6
text: The method of any of claims 1 to 5, wherein the recovery step (c) is performed at least 3 weeks after the administration step (a).
number: 7
text: The method of any of claims 1 to 6 further comprising the purification, expansion and/or activation of the lymphocytes obtained in step (c).
number: 8
text: The method of claim 7 wherein the expansion of the lymphocytes is carried out by stimulating the lymphocytes with a cytokine combination comprising IL-2, IL-15, and IL-21
number: 9
text: The method of claims 7 or 8 wherein the activation of the lymphocytes is carried using an anti-CD3 antibody in the presence of irradiated feeder cells.
number: 10
text: A cellular population of lymphocytes obtainable by the method of any of claims 1 to 9.
number: 11
text: The cellular population of claim 10, wherein the lymphocytes are tumor-specific T cells.
number: 12
text: The cellular population of any of claims 10 or 11 for use in the treatment of cancer.
number: 13
text: The cellular population for use according to claim 12 wherein the cancer is pancreatic cancer.
number: 14
text: The cellular population for use according to claims 12 or 13 wherein the patient is preconditioned by anti-tumor therapy prior to the administration of the cellular population of tumor infiltrating lymphocytes.
number: 15
text: A method for theex vivo activation of lymphocytes against a tumor found in subject, comprising:
Office action: search_report, dated 2017-10-11
Rejection reasons: novelty_epc_54
inventive_step_epc_56
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severity: novelty_destroying
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ref_type: npl
severity: background
Final disposition: pending (2017-10-11)