US 2025/0019772 A1 · Method and System of Augmenting Cancer Therapy

Abstract

Following DNA damage events, such as radiation therapy, cytosolic dsDNA species are generated that trigger intrinsic STimulator of Interferon Genes (STING) signaling and render cells competent for phagocytic activation contingent on the chemokine CCL5 (C-C Motif Ligand 5). Loss of STING signaling or inducible CCL5, rendered DNA-damaged cells incapable of APC stimulation following phagocytosis. STING signaling facilitated the generation of immunogenic endosomal vesicles comprising the autophagy related proteins RAB9 and LC3, and cytosolic DNA which triggered APC activation in trans, an event which also required extrinsic cGAS/STING-dependent signaling. Further, the combination of radiation treatment in the presence of type I IFN greatly reduced tumor growth while rescuing the ability to generate CTL activity. Reconstitution of STING signaling and/or the combination of radiation treatment in the presence of type I IFN could significantly augment cancer therapy.

Claims19

Dependent claims

A method of treating cancer in a subject in need thereof comprising administering a radiation therapy to the subject, where the subject has been determined to be responsive to the radiation therapy comprising:

(a) contacting a sample from the subject comprising one or more nucleic acid molecules with a device comprising a single-stranded nucleic acid molecule capable of specifically hybridizing with nucleotides of a CCL5 gene;
(b) detecting a level of expression of the CCL5 gene by performing microarray analysis or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) of the sample;
and
(c) determining that the CCL5 gene is expressed in the subject.

1 more element

Dependencies are inferred from the claim text.

Method and System of Augmenting Cancer Therapy

Life of this patent

Method and System of Augmenting Cancer Therapy

Life of this patent

Abstract

Claims19