Methods of using IL-21 for adoptive immunotherapy and identification of tumor antigens
First Claim
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1. A method of preparing a T cell population comprising:
- isolating peripheral blood mononuclear cells (PBMCs) from a biological sample;
identifying PBMCs having a histocompatible phenotype to a subject having a tumor;
selecting a CD8+ human T cell population from the identified PBMCs;
depleting CD45RO+ cells from the selected CD8+ human T cell population;
selecting CD62L+ cells from the CD45RO+ cells depleted CD8+ human T cell population to obtain a naï
ve CD8+ human T cell population having a phenotype of CD8+CD45RO-CD45RA+CD62L+,co-culturing tumor material isolated from the subject with the naï
ve CD8+ human T cell population in the presence of an IL-21 composition and antigen presenting cells (APCs); and
expanding the cells in culture.
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Abstract
Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.
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Citations
14 Claims
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1. A method of preparing a T cell population comprising:
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isolating peripheral blood mononuclear cells (PBMCs) from a biological sample; identifying PBMCs having a histocompatible phenotype to a subject having a tumor; selecting a CD8+ human T cell population from the identified PBMCs; depleting CD45RO+ cells from the selected CD8+ human T cell population; selecting CD62L+ cells from the CD45RO+ cells depleted CD8+ human T cell population to obtain a naï
ve CD8+ human T cell population having a phenotype of CD8+CD45RO-CD45RA+CD62L+,co-culturing tumor material isolated from the subject with the naï
ve CD8+ human T cell population in the presence of an IL-21 composition and antigen presenting cells (APCs); andexpanding the cells in culture. - View Dependent Claims (2, 3, 12)
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4. A method of preparing a naive CD8+ human T cell population comprising:
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obtaining a biological sample containing T cells; identifying a T cell population having a histocompatible phenotype to a subject having a tumor; selecting a CD8+ human T cell population from the identified T cell population; depleting CD45RO+ cells from the selected CD8+ human T cell population; selecting CD62L+ cells from the CD45RO+ cells depleted CD8+ human T cell population to obtain the naï
ve CD8+ human T cell population having a phenotype of CD8+CD45RO-CD45RA+CD62L+,co-culturing tumor material from the subject with the naive CD8+ human T cell population in the presence of an IL-21 composition and APCs; and expanding these cells in culture. - View Dependent Claims (5, 6, 7, 8, 9)
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10. A method of preparing a non-terminally differentiated CD8+ human T cell population for use in adoptive immunotherapy comprising:
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obtaining a biological sample containing T cells; identifying a T cell population having a histocompatible phenotype to a subject having a tumor; selecting a non-terminally differentiated CD8+ human T cell population from the identified T cell population; depleting CD45RO+ cells from the selected CD8+ human T cell population; selecting CD62L+ cells from the CD45RO+ cells depleted CD8+ human T cell population to obtain the non-terminally differentiated CD8+ human T cell population having a phenotype of CD8+CD45RO-CD45RA+CD62L+, co-culturing tumor material from the subject with the non-terminally differentiated CD8+ human T cell population in the presence of an IL-21 composition and APCs; and expanding these cells in culture. - View Dependent Claims (11, 13, 14)
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Specification