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Rational Design of Novel Anti-Cancer Therapeutic Proteins

FCCC Ref. No. 429-RD
 

Background

Ovarian cancer is diagnosed in roughly 239,000 women worldwide every year, including approximately 22,000 women in the United States. High mortality is the hallmark of the disease: the overall 5-year relative survival rate in the U.S. is 45%, and for the two thirds of women with distant or unstaged cancer at diagnosis, it is less than 27%. Despite the acute clinical need, ovarian cancer treatment has evolved very little in the past three decades, and mortality rates are relatively unchanged. Thus, development of new effective treatments is imperative.

The Mullerian-inhibiting substance type II receptor (MISIIR) is among the most promising diseaseassociated targets. MISIIR is co-expressed on the developing female reproductive tract along with its partner activin receptor-like kinase (ALK) Type I receptor, ALK2, ALK3, and/or ALKG. The natural ligand, the Mullerian-inhibiting substance (MIS) forms a ternary complex with MISIIR and ALK, activating signaling pathway and triggering apoptosis, leading to regression of the female reproductive tract. MISIIR is expressed at moderately high levels in 70% of epithelial ovarian cancers, which account for 90% of all ovarian cancers, and in a wide variety of other gynecological cancers, as well as some breast and prostate cancers.

Summary of the Invention

Researchers at Fox Chase Cancer Center developed rationally recombinant proteins that consist of a bone morphogenic protein 2 backbone onto which a Mullerian-inhibiting substance type II receptor binding region of the Mullerian-inhibiting substance protein was grafted. The chimera proteins have the ability to bind to and stimulate MISIIR, and ALK2, ALK3, and/or ALK6 on the surface of a cell in order to induce apoptosis. These novel proteins are envisioned promising therapeutics in the treatment of cancers such as ovarian, uterine, endometrial, fallopian tube, breast, prostate, and lung cancers.

Advantages

  • Novel target-based cancer therapy
  • Rational design of proteins binding to cancer cell surface receptors assures high specificity
  • Use for treating ovarian, uterine, endometrial, fallopian tube, breast, prostate, and lung cancers IP Status

Patent application filed

For licensing/partnering information, please contact:
Inna Khartchenko, MS, MBA
Director, Technology Transfer
E-mail: Inna.Khartchenko@fccc.edu

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