Methods and compositions for T-cell coculture potency assays and use with cell therapy products
AssigneeIovance Biotherapeutics, Inc.
InventorsMichelle R. Simpson-Abelson, Matthew J. Frigault, Wayne P. Rothbaum, Michael Weiser
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Abstract
The present invention provides novel processes, compositions, and methods for analyzing or assaying the potency and/or functionality of tumor infiltrating lymphocyte (TIL) products for use in therapy, including human cancer therapy, and analyzing or assaying the potency and/or functionality of other polyclonal products, such as marrow infiltrating lymphocyte (MIL) and peripheral blood lymphocyte (PBL) products. Compositions, methods, and kits for preparing and treating cancer using TIL, MIL, and PBL products are also provided.
Claims28
A method of determining the potency of a tumor infiltrating lymphocyte (TIL) cell product comprising TIL cells, the method comprising the steps of:
- i. performing at least three co-cultures of U937 target cells with TIL cell product cells at different U937 target cell concentrations;
- ii. performing at least three co-cultures of U937 target cells with T cell reference standard cells at different U937 target cell concentrations;
- iii. extracting supernatants from each of the co-cultures;
- and
- iv. assessing the supernatants for interferon-gamma (IFN-γ) secreted from the TIL cell product cells and T cell reference standard cells to obtain U937 target cell dose-concentrations to determine the potency of the TIL cell product;
- wherein the U937 target cells express a major histocompatibility complex (MHC) and the TIL cells express a T cell receptor (TCR), wherein the TIL cells are activated via allogeneic MHC-TCR engagement between the MHC of the U937 target cells and the TCR of the TIL cells during the co-culture assay.
A method for treating cancer in a patient in need thereof, the method comprising:
- a) providing a therapeutic population of tumor infiltrating lymphocytes (TILs) expanded from a tumor resected from the patient;
- b) determining the potency of the population of TILs by:
- i) performing at least three co-cultures of U937 target cells with a subset of the therapeutic population of TILs at different U937 target cell concentrations;
- ii) performing at least three co-cultures of U937 target cells with T cell reference standard cells at different U937 target cell concentrations;
- iii) extracting supernatants from each of the co-cultures;
- and
- iv) assessing the supernatants for interferon-gamma (IFN-γ) secreted from the subset of the therapeutic population of TILs and T cell reference standard cells to obtain U937 target cell dose-concentrations to determine the potency of the therapeutic population of TILs;
- wherein the U937 target cells express a major histocompatibility complex (MHC) and the TIL cells express a T cell receptor (TCR), wherein the TIL cells are activated via allogeneic MHC-TCR engagement between the MHC of the U937 target cells and the TCR of the TIL cells during the co-culture assay;
- and
- c) administering a therapeutically effective dosage of the therapeutic population of TILs to the patient.
Dependencies are inferred from the claim text.