Claims for Patent: 10,072,246
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Summary for Patent: 10,072,246
| Title: | Enhanced generation of cytotoxic T lymphocytes by IL-21 mediated FoxP3 suppression |
| Abstract: | A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described. |
| Inventor(s): | Yee; Cassian (Seattle, WA), Li; Yongqing (Shoreline, WA) |
| Assignee: | The Fred Hutchinson Cancer Research Center (Seattle, WA) |
| Application Number: | 15/188,096 |
| Patent Claims: | 1. A method of making a cytotoxic T lymphocyte (CTL) preparation useful for adoptive immunotherapy, comprising: (a) sorting a lymphocyte subpopulation depleted of
CD25.sup.+ cells from a first lymphocyte population of peripheral blood mononuclear cells (PBMC) to produce a CD8.sup.+CD25.sup.-subpopulation; (b) promoting the production of antigen-specific CTL cells in said subpopulation by in vitro culturing the
sorted CD8.sup.+CD25.sup.- subpopulation with antigen in a medium containing interleukin-21; and (c) formulating antigen-specific CTL cells produced therefrom into a pharmaceutical formulation.
2. The method of claim 1, wherein said interleukin-21 is included in said culture in an amount of from 1 to 1000 nanograms per milliliter. 3. The method of claim 1, wherein the CTL cells are specific for a tumor antigen. 4. The method of claim 1, wherein (a) the sorting a lymphocyte subpopulation depleted of CD25.sup.+ cells from a first lymphocyte population comprises treating the first lymphocyte population with denileukin diftitox. 5. The method of claim 1, wherein (a) the sorting a lymphocyte subpopulation depleted of CD25.sup.+ cells from a first lymphocyte population comprises contacting the first lymphocyte population with anti-CD25 antibodies. 6. The method of claim 1, wherein (b) the promoting the production of antigen-specific CTL cells in said subpopulation by in vitro culturing comprises culturing the CTLs with antigen presenting cells. 7. The method of claim 1, wherein the antigen presenting cells comprise dendritic cells (DCs). 8. The method of claim 1, wherein the antigen-specific CTL cells comprise a transgene. 9. The method of claim 1, wherein the antigen-specific CTL cells of the formulation consist essentially of CD8.sup.+CD25- antigen-specific CTL cells. 10. The method of claim 1, wherein the number of antigen specific CTL are enriched in said CD8.sup.+CD25.sup.- subpopulation by at least 100-fold, as compared to that seen in the same lymphocyte population not subjected to either the sorting step (a) or the promoting step (b). 11. The method of claim 1, wherein the pharmaceutical formulation comprises at least 10.sup.9 CTL cells. |
Details for Patent 10,072,246
| Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
|---|---|---|---|---|---|---|---|
| Eisai, Incorporated | ONTAK | denileukin diftitox | Injection | 103767 | February 05, 1999 | ⤷ Try for Free | 2027-10-03 |
| >Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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