Johns Hopkins University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Richard B Roden

Ravi K Anchoori

Balasubramanyam Karanam

John T Schiller

Douglas R Lowy

Diana V Pastrana

Ratish Gambhira

Subhashini Jagu

We describe a bis-benzylidine piperidone, RA190, which covalently binds to the ubiquitin receptor RPN13 (ADRM1) in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma lines, even those resistant to bortezomib, were sensitive to RA190 via ER stress-related apoptosis. RA190 stabilized targets of human papillomavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed cells. After p.o. or i.p. dosing of mice, RA190 distributed to plasma and major organs excepting brain, and potently inhibited proteasome function in skin and muscle. RA190 administration i.p. profoundly reduced growth of multiple myeloma and ovarian cancer xenografts, and oral RA190 treatment retarded HPV+ syngeneic mouse tumor growth, without impacting spontaneous HPV-specific CD8+ T cell responses, suggesting its therapeutic potential. The bis-benzylidine piperidone RA190 is a new orally-available proteasome inhibitor. Multiple myeloma, cervical and ovarian cancers are particularly sensitive to RA190.

Bis-benzylidine piperidone proteasome inhibitor with anticancer activity

Embodiments of the invention are directed to methods and compositions of multitype HPV polypeptides.

Multitype HPV peptide compositions and methods for treatment or prevention of human papillomavirus infection

The invention provides an infectious papillomavirus pseudoviral particle useful in gene transfer comprising: (a) a papillomavirus vector DNA which comprises an E2 binding site and an expression cassette comprising a gene and a sequence controlling expression of said gene; and (b) a papillomavirus capsid which comprises L1 and L2 structural proteins, such that said capsid encapsidates said vector DNA, wherein said gene is derived from a first biological species and said L1 structural protein is derived from a second biological species and said first biological species is different from said second biological species.

Infectious papillomavirus pseudoviral particles

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Severna Park, MD, United States of America

Richard B Roden