Methods of using ERBB2 conjugate peptides

Inventors

Mei, Lin • XIONG, WEN-CHENG • Shen, Cheng-Yong • Tao, Yan-Mei • Luo, Shi-Wen

Assignees

Augusta University • Augusta University Research Institute Inc

Abstract

Compositions that inhibit or block the interaction between Erbin and ErbB2 and methods of their use are provided. Preferred compositions include peptides that inhibit or block Erbin and ErbB2 interaction under physiologic conditions in a subject. One embodiment provides an isolated peptide fragment of ErbB2 including the C-terminal 15 amino acids of ErbB2. The peptide fragment can be about 15 to 27 amino acids in length.

Core Innovation

The disclosure describes ErbB2/ERBB2-targeting peptide compositions that inhibit or block the Erbin-ErbB2 interaction. It provides an ErbB2 C-terminal PDZ-binding fragment and a conjugate in which the fragment is linked to a TAT transduction domain. The compositions are characterized in the context of disrupting the interaction between Erbin and ErbB2.

The problem addressed is that Erbin-ErbB2 interaction is associated with ErbB2-dependent tumor cell growth and related ErbB2 functions. The disclosure states that disruption of the ErbB2 PDZ-domain interaction impairs ErbB2 stability, signaling, and tumor cell growth in ErbB2-dependent cancer. It further frames the approach as targeting ErbB2/Erbin complex formation to interfere with ErbB2-dependent phenotypes.

The disclosure supports the concept with described in vivo and in vitro findings. Erbin loss delays or inhibits ErbB2-dependent tumorigenesis in MMTV-neu mice, and Erbin knockdown suppresses ErbB2-dependent proliferation and DCIS-like lumen invasion. It also describes that ErbB2 PDZ-domain disruption using B2tail/TAT-B2tail reduces ErbB2 stability and proliferation in cell models and suppresses tumor growth in nude mice, and it correlates elevated Erbin with ErbB2-overexpressing human breast tumors.

Claims Coverage

The identified independent claims each describe administering an effective amount of the specific conjugate ErbB2 peptide of SEQ ID NO:2, with one independent claim directed to treating ErbB2-dependent cancer and the other directed to decreasing ErbB2-dependent growth of cancer cells. Across both independent claims, the inventive focus is on the SEQ ID NO:2 conjugate delivered by administration to achieve ErbB2-dependent therapeutic and growth effects.

Both independent claims center on administration of the conjugate ErbB2 peptide of SEQ ID NO:2 to produce outcomes tied to ErbB2-dependent cancer biology, namely treating ErbB2-dependent cancer and decreasing ErbB2-dependent growth of cancer cells.

Stated Advantages

Documented Applications