Small molecule cytokine conjugates for cancer trea.. (SMCCCTHER)
Small molecule cytokine conjugates for cancer treatment
Start date: Aug 1, 2014,
End date: Jul 31, 2016
Standard of care strategies for the treatment of cancer still relies heavily on non-specific radiation- and chemotherapy. They are commonly associated with severe toxicities and in many cases only offer limited benefit for the patient. The targeted delivery of radionuclides, cytotoxic drugs and proinflammatory cytokines into malignant tissue, on the other hand, can markedly improve the therapeutic index and overall efficacy of such substances. Whilst monoclonal antibodies are the most widely used delivery vehicles to date, we believe that small molecule ligands will offer improved targeting properties. Most importantly, depth of tumour penetration and tumour-to-blood distribution ratio after injection should be significantly superior. We therefore propose to systematically investigate the targeting performance of somatostatin receptor non-internalizing ligands for the targeted delivery of cytokines into somatostatin receptor-overexpressing tumours. This project aims at (1) developing a general chemical approach for building safe small molecule cytokine conjugates (SMCC) (2) demonstrate that a somatostatin antagonist, non-internalizing ligand can selectively accumulate in somatostatin receptor-overexpressing cancers and (3) when site-specifically conjugated to proinflammatory interleukin-12, these novel SMCC are highly effective for the treatment of acute myeloid leukaemia (AML).
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