EX VIVO USE OF MODIFIED CELLS OF LEUKEMIC ORIGIN FOR ENHANCING THE EFFICACY OF ADOPTIVE CELL THERAPY
The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.
1 - 123 . (canceled)
124 . A method for generating and/or expanding a population of immune cells with enhanced activation status, comprising:
(a) obtaining a population of immune cells from a subject;
(b) contacting the population of immune cells with a non-proliferating modified cell of leukemic origin having a mature dendritic cell phenotype;
and
(c) co-culturing the population of immune cells and the modified cell of leukemic origin under conditions suitable to expand and stimulate proliferation of the immune cells,
thereby generating the population of immune cells with enhanced activation status, wherein the method results in multiplying the population of immune cells by at least 10 fold.
125 . The method of claim 124 , wherein the modified cell of leukemic origin is CD40-positive, CD80-positive, and CD86-positive; and optionally wherein the modified cell of leukemic origin comprises a CD70 costimulatory molecule.
126 . The method of claim 124 , wherein the modified cell of leukemic origin is a cell derived from cell line DCOne as deposited under the conditions of the Budapest treaty with the DSMZ under accession number DSMZ ACC3189 on 15 Nov. 2012.
127 . The method of claim 124 , wherein the immune cells comprises memory T cells, memory B cells, and/or natural killer cells.
128 . The method of claim 124 , wherein the population of immune cells are modified to express a chimeric antigen receptor (CAR) which binds a tumor antigen on a tumor cell in the patient.
129 . The method of claim 124 , wherein the population of immune cells are obtained from a patient suffering from cancer.
130 . The method of claim 129 , wherein the population of immune cells are obtained from peripheral blood mononuclear cells (PBMCs) of the patient suffering from a cancer.
131 . The method of claim 124 , wherein the population of immune cells are obtained from a healthy donor subject.
132 . The method of claim 124 , wherein the population of immune cells comprise T cells.
133 . The method of claim 132 , wherein T cells are obtained from circulating blood of an individual.
134 . The method of claim 132 , wherein the population of T cells comprise both CD4+ and CD8+ cells, and the method results in an increased ratio of CD4+ to CD8+ cells.
135 . The method of claim 132 , wherein the increased ratio of CD4+ to CD8+ cells is between at or about 1:5 and at or about 5:1.
136 . The method of claim 132 , wherein the increased ratio of CD4+ to CD8+ cells is between at or about 1:3 and at or about 3:1.
137 . The method of claim 124 , wherein the modified cell of leukemic origin comprises an exogenous antigen or peptide fragments of the exogenous antigen, wherein the exogenous antigen is a tumor-associated antigen (TAA) or non-tumor-associated antigen.
138 . The method of claim 137 , wherein the modified cell of leukemic origin is loaded with the exogenous antigen or peptide fragments thereof prior to its exhibiting a mature dendritic cell phenotype, during transition of the modified cell of leukemic origin to a mature dendritic cell phenotype, or after the modified cell of leukemic origin exhibits a mature dendritic cell phenotype.
139 . The method of claim 124 , wherein the population of immune cells are modified to express a chimeric antigen receptor (CAR) which binds the exogenous antigen or peptide fragments thereof displayed on the modified cell of leukemic origin.
140 . A method for treating a patient suffering from the cancer, and the method comprising administering to the patient suffering from the cancer the population of immune cells with enhanced activation status generated and expanded by the method of claim 124 .
141 . The method of claim 140 , wherein the population of immune cells with enhanced activation status are autologous to the patient that is administered the immune cells.
142 . The method of claim 140 , wherein the cancer comprises a liquid tumor.
143 . The method of claim 140 , wherein the cancer comprises a solid tumor.