Treating Cancer Using Novel Methods Employing Adenovirus Fragments

SLU ID 11-015 | Using Adenovirus E1A Fragments for Cancer Therapies

Background

Up-regulation of the HER2/neu (erbB2) proto-oncogene occurs in several types of human cancer, including breast, ovary, and prostate. For example, HER2 up-regulation in breast cancer is predictive of aggressive disease with a poor prognosis. Approximately 25-30 percent of breast cancers are positive for HER2 up-regulation but account for 60-80 percent of breast cancer deaths. Several studies with human cancer cell lines have shown that although they may have acquired multiple genetic and epigenetic abnormalities, they can remain highly dependent on the expression of a single oncogene for cell proliferation and survival. The Ad group C (types 2 and 5) E1A oncogene encodes two major proteins of 243 and 289 amino acid residues (243R and 289R) which contain multiple functional domains that interact with key cellular regulatory factors. E1A is involved in diverse functions, including transcriptional activation, induction of cellular DNA synthesis, cell immortalization, cell transformation, and of particular interest, transcriptional-repression. The Ad5 oncogene inhibits the expression of HER2 in rodent and human cell cultures. However, the full length Ad E1A oncogene is not a good candidate as a therapy because it possesses, in addition to its transcription-repression function, other biological activities which may complicate a medical therapy and could have long-term deleterious effects. Further, other E1A domains interact with several important cellular proteins not associated with its transcriptional repression function, which can have profound effects on cell cycle regulation.

Overview

Researchers at Saint Louis University have developed an improved cancer therapy utilizing a fragment of adenovirus E1A that represses transcription of oncogenic genes such as HER2/Neu. They have demonstrated that the E1A repression domain (a recombinant protein containing only the N-terminal 80 amino acids) exhibits the same repression function as the entire E1A 243R oncoprotein thus avoiding biological activities that could negatively impact a medical therapy.

Benefits

The potential benefits of this technology include:

• Increasing the effectiveness of existing cancer therapies

• Increasing the effectiveness of treatments of HER2 oncogene addicted cancers

• Increasing the number of options for treating cancers

Applications

This technology has several potential applications including:

• Breast cancer therapies

• Brain cancer treatments

• Ovarian cancer therapies

• Prostate cancer therapies

• Carcinoma, adenocarcinoma, and glioblastoma

• Multi-drug resistant cancer

• Molecular biology

Opportunity

Saint Louis University is seeking a partner to further develop and commercialize this technology.