In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 15_Supplement ( 2016-08-01), p. IA12-IA12
Abstract:
This laboratory studies tissue-specific vascular markers, “vascular zip codes”, and their use in selective targeting of drugs to diseased tissues. Screening of phage libraries in live mice identifies peptides that direct phage homing to a specific target in the body. When the libraries are injected into the circulation, tissue-specific or tumor-specific differences in endothelial cells are primarily targeted. The endothelial target molecules are frequently also expressed by other tumor stromal cells and tumor cells, but not cells in normal tissues. Recently discovered tumor-penetrating peptides, through a complex mechanism that involves a proteolytic cleavage and binding to a second receptor, activate an endocytic transport pathway related to but distinct from macropinocytosis. This trans-tissue pathway, dubbed the CendR pathway, mediates the exit of payloads ranging from small molecule drugs to nanoparticles from the blood vessels and transport through extravascular tumor tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a drug, antibody, or nanoparticle payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Remarkably the payload does not have to be coupled to the peptide; the peptide activates a bulk transport system that sweeps along any compound that is present in the blood. Treatment studies in mice show improved anti-tumor efficacy and less damage to normal tissues. Citation Format: Erkki Ruoslahti, Erkki Ruoslahti. Stromal cells in the targeting and transport of tumor-penetrating peptides. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA12.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.TME16-IA12
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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