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Last Updated: January 26, 2022

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Claims for Patent: 7,993,638

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Summary for Patent: 7,993,638
Title:Cancer treatment combining lymphodepleting agent with CTLs and cytokines
Abstract: In a cancer treatment combining cell therapy with chemotherapy, autologous CD8.sup.+ T cells are obtained from a patient, activated ex vivo by contacting them with xenogenic antigen presenting cells loaded with selected peptide antigen, thereby generating antigen-specific activated cytotoxic T lymphocytes. Such activated CTLs are administered to the patient in conjunction with a lymphodepletion and CTL maintenance regimen comprising a non-myeloblative but lymphdepleting agent, such as cladribine or denileukin diftitox, and interleukin-2 and interferon-.alpha.-2b stimulatory cytokines.
Inventor(s): Cai; Zeling (San Diego, CA), Moriarty; Ann (Poway, CA), Peterson; Per A. (Rancho Santa Fe, CA), Richards; Jon M. (Glenview, IL)
Assignee: Janssen Pharmaceutica NV (BE)
Application Number:12/281,197
Patent Claims:1. A method for treating a subject in need of treatment for cancer, comprising: (a) obtaining naive CD8+T cells from the subject; (b) contacting the naive CD8+T cells ex vivo with xenogenic antigen presenting cells loaded with one or more peptide antigens, thereby generating activated CTLs that target cells expressing said one or more peptide antigens; (c) administering to the subject the activated CTLs; (d) administering to the subject at least two cytokines that effect CTL persistence; and (e) administering to the subject a lymphodepleting agent selected from the group consisting of cladribine and denileukin diftitox.

2. A method as defined in claim 1, wherein said at said at least two cytokines comprise interferon-.alpha.-2b and interleukin-2.

3. A method as defined in claim 2, wherein said one or more peptide antigens comprise an amino acid sequence derived from a protein selected from gp100, tyrosinase, and MART-1.

4. A method as defined in claim 1, wherein said one or more peptide antigens consists of peptide antigens derived from human gp100, tyrosinase, and MART-1 proteins.

5. A method as defined in claim 1, wherein each of said one or more peptide antigens is selected from the group consisting of YMNGTMSQV (SEQ ID NO:1), YMDGTMSQV (SEQ ID NO:2), AAGIGILTV (SEQ ID NO:3), ITDQVPFSV (SEQ ID NO:4), YLEPGPVTA (SEQ ID NO:5), and KTWGQYWQV (SEQ ID NO:6).

6. A method as defined in claim 5, wherein said cancer is a melanoma.

7. A method as defined in claim 1, wherein the administration of the lymphodepleting agent begins before the administration of the activated CTLs.

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