Generation of HPV-specific T-cells
AssigneeBaylor College of Medicine
InventorsCarlos A. Ramos, Cliona M. Rooney, Neeharika Narala
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Abstract
Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.
Claims15
A method of treating a human papillomavirus (HPV)-positive cancer in a subject, the method comprising:
- (1) generating or expanding a population of T cells specific for a HPV by a method comprising:
- (a) obtaining peripheral blood T-cells from a subject with HPV-positive cancer;
- and (b) stimulating the peripheral blood T-cells with antigen presenting cells in the presence of interleukin (IL)-7 and IL-15 and in the absence of IL-6 and/or IL-12, wherein the antigen presenting cells were previously exposed to one or more peptides, wherein the peptides comprise sequence that corresponds to at least 8 contiguous amino acids of the sequence of one or both of E6 and E7 of HPV;
- and (2) administering the generated or expanded population of T cells to a subject with HPV-positive cancer.
A method of treating a HPV-positive cancer in a subject, the method comprising:
- (1) generating or expanding a population of T cells specific for a HPV by a method comprising:
- (i) (a) obtaining peripheral blood T-cells from a subject with HPV-positive cancer;
- and (b) stimulating the peripheral blood T-cells with antigen presenting cells in the presence of interleukin (IL)-7 and IL-15, wherein the antigen presenting cells were previously exposed to one or more peptides, wherein the peptides comprise sequence that corresponds to at least 8 contiguous amino acids of the sequence of one or both of E6 and E7 of HPV;
- (ii) stimulating the peripheral blood T-cells obtained from (i) with antigen presenting cells in the presence of interleukin (IL)-7 and IL-15 and in the absence of IL-6 and/or IL-12, wherein the antigen presenting cells were previously exposed to one or more peptides, wherein the peptides comprise sequence that corresponds to at least 8 contiguous amino acids of the sequence of one or both of E6 and E7 of HPV, wherein (ii) is optionally repeated one or more times;
- and
- (iii) stimulating T-cells obtained from (ii) with antigen presenting cells in the presence of interleukin (IL)-7 and IL-15, and in the presence of co-stimulatory cells, wherein the antigen presenting cells were previously exposed to one or more peptides, wherein the peptides comprise sequence that corresponds to at least 8 contiguous amino acids of the sequence of one or both of E6 and E7 of HPV, wherein (iii) is optionally repeated one or more times;
- (2) administering the generated or expanded population of T cells to a subject with HPV-positive cancer.
A method of treating a cancer in a HPV-positive subject, the method comprising:
- (1) generating or expanding a population of T cells specific for a HPV by a method comprising:
- (a) obtaining peripheral blood T-cells from a subject with HPV-positive cancer;
- and (b) stimulating T-cells specific for HPV or for an HPV antigen in the peripheral blood with antigen presenting cells in the presence of IL-7 and IL-15 and in the absence of IL-6 and/or IL-12 and in the presence of co-stimulatory cells, wherein the antigen presenting cells were previously exposed to one or more peptides, wherein the peptides comprise sequence that corresponds to at least 8 contiguous amino acids of the sequence of one or both of E6 and E7 of HPV;
- and
- (2) administering the generated or expanded population of T cells to a subject with HPV-positive cancer.
Dependencies are inferred from the claim text.