Methods for producing a super central memory cd8 t cell subtype by poly(adp-ribose) polymerase (parp) inhibition and uses thereof
AssigneeGeorgetown University
InventorsSamir N. Khleif, Seema Gupta, Wael Traboulsi
Life of this patent
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Abstract
A unique CD8 T cell central memory subtype obtained by treatment of CD8 T cells with a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) is described. These cells, referred to as super-central memory CD8 T cells (TCMsup) or PARPi-induced memory T cells, are significantly more efficient for cancer therapy than traditional central memory T cells (TCM) generated by tumor antigens. Methods of using the TCMsup cells for enhancing cancer immunotherapy, enhancing vaccine-induced immunity, and treating cancer are described.
Claims49
An ex vivo method of producing super central memory CD8+ T cells that express CD62L and CD44, CD45RO and CD62L, or CD45RO and CCR7, comprising culturing CD8+ T cells in the presence of a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi), thereby generating super central memory CD8+ T cells that express CD62L and CD44, CD45RO and CD62L, or CD45RO and CCR7.
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A method of treating a cancer in a subject, comprising:
- culturing CD8+ T cells ex vivo with a PARP inhibitor (PARPi), thereby producing super central memory CD8+ T cells that express CD62L and CD44, CD45RO and CD62L, or CD45RO and CCR7;
- and
- adoptively transferring the super central memory CD8+ T cells to the subject, thereby treating the cancer in the subject.
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A method of enhancing an immune response to a vaccine in a subject, comprising:
- administering to the subject the vaccine and a therapeutically effective amount of a PARP inhibitor (PARPi);
- or
- administering to the subject the vaccine and a therapeutically effective amount of super central memory CD8+ T cells that express CD62L and CD44, CD45RO and CD62L, or CD45RO and CCR7.
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A method of treating a cancer in a subject, comprising:
- administering to the subject an immunotherapy and a therapeutically effective amount of a PARP inhibitor (PARPi), thereby treating the cancer in the subject;
- or
- administering to the subject an immunotherapy and a therapeutically effective amount of super central memory CD8+ T cells that express CD62L and CD44, CD45RO and CD62L, or CD45RO and CCR7.
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Dependencies are inferred from the claim text.