University of California

Sanford-burnham Medical Research Institute

Burnham Institute for Medical Research

The United States of America As Represented by the Secretary of Health

Douglas Hanahan

Erkki I Ruoslahti

Lianglin Zhang

Jeffrey M Arbeit

Joe W Gray

Peter M Howley

Jeffrey H Hager

Pirjo Laakkonen

Keith R Yamamoto

Graeme Hodgson

Oriol Casanovas

Maria D Vivanco

Johanna A Joyce

Disclosed herein are compositions and methods for and involving selectively targeting tumor lymphatics.

Lymphatic zip codes in tumors and pre-malignant lesions

The present invention provides a conjugate that contains a therapeutic moiety linked to a homing peptide or peptidomimetic which selectively homes to vasculature of pre-malignant dysplastic skin and which includes the amino acid sequence SRPRR (SEQ ID NO: 1) or a conservative variant or peptidomimetic thereof. The present invention further provides a conjugate containing a therapeutic moiety linked to a homing peptide or peptidomimetic which selectively homes to vasculature of malignant skin and which includes the amino acid sequence CGKRK (SEQ ID NO: 6) or the amino acid sequence CDTRL (SEQ ID NO: 7), or a conservative variant or peptidomimetic of one of these sequences.

Molecules that selectively home to vasculature of pre-malignant dysplastic lesions or malignancies

This invention provides methods employing prefoldin-4 (PFDN-4) nucleic acid and polypeptide sequences to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and/or for prognostic applications. Further, the invention provides methods of identifying inhibitors of PfDN-4 and methods of treating cancer by inhibiting the expression and/or activity of PFDN-4.

Prefoldin 4 in the treatment and diagnosis of cancer

The invention provides a conjugate that includes a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to vasculature of premalignant pancreas. The peptide or peptidomimetic contains at least 5 contiguous amino acids of an amino acid sequence selected from CRSRKG (SEQ ID NO:9) and CEYQLDVE (SEQ ID NO:34), or a conservative variant or peptidomimetic thereof. The invention additionally provides a conjugate containing a therapeutic moiety linked to a peptide or peptidomimetic that selectively homes to pancreatic tumor cells and pancreatic tumor vasculature, the peptide or peptidomimetic comprising at least 5 contiguous amino acids of an amino acid sequence selected from CKAAKNK (SEQ ID NO:15), CKGAKAR (SEQ ID NO:19), and VGVGEWSV (SEQ ID NO:35), or a conservative variant or peptidomimetic thereof.

Molecules that selectively home to vasculature of premalignant or malignant lesions of the pancreas and other organs

The present invention relates to improved models for progressive epithelial neoplasias and methods for their use. In particular, the invention provides transgenic mice comprising a human papilloma virus early region oncogene operably linked to a promoter which directs expression of the oncogene in a transient amplifying cell in the mice.

Transgenic mice expressing HPV early region oncogene develop progressive

Intracellular hormone receptors are discovered to undergo posttranslational regulation. Assays to assess cancer progression and to permit discovery of a new class of biologically active compounds are provided. Related kits are also provided.

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San Francisco, CA, United States of America

Douglas Hanahan