Abstract
The disclosure provides methods of performing adoptive cell transfer using IL-15, where the methods are performed without lymphodepletion of the subject.
Claims
- WHAT IS CLAIMED IS: 1. A method of increasing adoptive cell therapy efficacy in a subject that does not undergo a lymphodepletion procedure, the method comprising:
- administering a heterodimeric IL-15/IL-15 receptor alpha complex (hetIL-15) to the subject;
- administering adoptive cell transfer (ACT) cells to the subject, wherein hetlL- 15 is administered at a frequency and in an amount that increases the number of lymphocytes present in the tumor. 2. The method of claim 1, wherein hetIL-15 is administered for at least 10 days. 3. The method of claim 1 , wherein het IL- 15 is administered every day. 4. The method of claim 2, wherein het IL-15 is administered every day. 5. The method of claim 1 , wherein hetIL- 15 is administered at two-day intervals or at three-day intervals. 6. The method of claim 2, wherein hetIL-15 is administered at two-day intervals or at three-day intervals 7. The method of one of claims 1 to 6, wherein the ACT cell comprise CD8+ lymphocytes. 8. The method of one of claims 1 to 6, wherein the ACT cell comprise Natural Killer cells. 9. The method of any one of claims 1 to 8, wherein the ACT cells are genetically modified to enhance anti-tumor effects. 10. The method of any one of claims 1 to 9, wherein hetIL-15 is administered subcutaneously.
- The method of any one of claims 1 to 9, wherein hetIL- 15 administered intravenously.
- The method of any one of claims 1 to 11, wherein the IL-15 receptor alpha present in hetIL-15 comprises soluble IL-15 receptor alpha form that is not fused to an Fc region. 13. The method of any one of claims 1 to 11, wherein the IL-15 receptor alpha present in het IL-15 comprises an IL-15 receptor alpha-Fc fusion polypeptide. 14. The method of any one of claims 1 to 13, wherein the subject is a human.
Applicants
Inventors
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Pavlakis George N
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Felber Barbara K
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Bergamaschi Cristina
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CPC Classifications
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A61K35/17
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A61K9/0019
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A61K38/1793
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A61K38/2086
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A61P35/00
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C07K14/5443
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C07K14/7155
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C07K19/00
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C07K2319/00
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C12N5/10
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C12N15/62
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C12N15/85
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Document History
- Publication: Oct 12, 2017
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Application:
Apr 6, 2017
US 2017/0026447 W
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Priority:
Dec 8, 2016
US 201662497948 P
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Priority:
Apr 6, 2016
US 201662319259 P