Tumor selective chemokine modulation

Abstract

Therapies effective for the treatment and prevention of cancer and other diseases are disclosed herein. These methods include the administration of therapeutically effective amounts of agents that increase the local production of effector cell-attracting chemokines within tumor lesions, with concommittant suppression of local production of undesirable chemokines that attract regulatory T(reg) cells. These methods include administering to the subject therapeutically effective amounts of a Toll-like receptor (TLR) agonist or other activator of NF-kB pathway in combination with a blocker of prostaglandin synthesis or a blocker of prostaglandin signaling, in combination with a type-1 interferon, or in combination with both a blocker of prostaglandin synthesis or signaling and with a type-1 interferon, thereby treating or preventing cancer or an infectious disease, or preventing their recurrence in the subject. Alternatively, the methods derived from the same paradigms, but aimed to treat or prevent autoimmune disease, chronic inflammatory disease, transplant rejection or GvH, include the combination of a Toll-like receptor (TLR) agonist in combination with a prostaglandin or other cAMP-activator.

Description

priority statement This application claims priority to US Provisional Application No. 61 / 510,855, filed July 22, 2011, which is incorporated herein by reference. statement of government support This invention was made with United States Government support under Grant 1PO1CA132714 awarded by the National Institutes of Health, which has certain rights in this invention. technical field The present application relates to the field of tumor treatment, including methods for treating cancer, preventing cancer occurrence or preventing cancer recurrence. In addition, the methods can be used in the treatment of infectious diseases, autoimmune diseases, allergies and inflammation, as well as in the treatment or prevention of transplant rejection and transplant-related disorders. Background technique Countless people in the United States alone develop precancerous lesions, a type of neoplastic tumor, each year, as discussed below. Such lesions show a strong tendency to develop ...

AI Technical Summary

Problems solved by technology

However, so far it is not known how to exploit the mode of NF-κB signaling and modulate it to enhance T selectively, or at least preferentially, in tumor tissue rather than marginal tissue. eff Production of attractive chemokines to selectively target T eff Cells direct to tumor

Images