[mtwalsh01]

A study published on October 31st in the Journal Advanced Functional Materials describes a Vitamin E-based hydrogel that facilitates sustained delivery of the Roche breast cancer drug Herceptin. The hydrogel was developed by a team from the IBM Almaden Research Center, San Jose, in the USA and in the Institute of Bioengineering and Nanotechnology in Singapore, who consider that it has potential for more general applicability in subcutaneous, sustained delivery of antibodies.

Herceptin (trastuzumab) is an anti-HER2 (ErbB2) receptor monoclonal antibody. HER2 is a member of the epidermal growth factor receptor (ErbB; EGFR) family, which is the pathway most explored as a next-generation breast cancer therapy target. HER2 is overexpressed in 20% to 25% of breast cancer cases and is associated with poor prognosis. Herceptin treatment has been shown to dramatically reduce relapse rates in these patients, although a subset of patients display primary drug resistance while many patients who initially respond to Herceptin ultimately suffer disease progression. The FDA has approved use of Herceptin in combination with other anti-HER2 agents such as pertuzumab, and docetaxel.

The current study in Advanced Functional Materials addressed the issue of patient compliance by potentially reducing the number and duration of the Herceptin antibody injections from the currently required weekly regime to a possible monthly schedule. ‘ABA’-type triblock copolymers composed of vitamin E-functionalized polycarbonate and poly(ethylene glycol), i.e., VitEm-PEG-VitEm, were used to make the injectable hydrogels. In vitro, the Herceptin-loaded hydrogels were shown to target HER2-overexpressing cancer cell lines as opposed to normal or other breast cancer cell lines. Cytotoxicity was comparable to that of Herceptin solution. In vivo, in BT474 HER2-loaded tumour-bearing mice, a single subcutaneous injection of Herceptin-loaded hydrogel near the tumour enhanced Herceptin retention and resulted in an anti-tumour effect which was superior to that of intravenous or subcutaneous Herceptin solution delivery. Even if the hydrogel was delivered distal to the tumour, the anti-tumour effect was comparable to that of weekly Herceptin intravenous injections over four weeks.

Thus this research offers a potential breakthrough in drug delivery and patient compliance not only in relation to Herceptin but also in delivery of antibody-based therapies in other diseases. The IBM research leader Yi Yan Yang stated "… our approach may help to improve patient compliance, offering a better alternative to existing breast cancer treatments. This technology can also be used to deliver other types of antibodies or proteins to treat different diseases." Currently, the researchers have filed a patent for their hydrogel technology and are seeking pharmaceutical partners in order to further the development of the hydrogel for clinical use.

Sources

BLUMENTHAL, G.M. et al., 2013. First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Clinical Cancer Research: An Official Journal Of The American Association For Cancer Research, 19(18), pp. 4911-4916

CHUNG, A. et al., 2013. Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance. Clinical Breast Cancer, 13(4), pp. 223-232

JELOVAC, D. and EMENS, L.A., 2013. HER2-directed therapy for metastatic breast cancer. Oncology (Williston Park, N.Y.), 27(3), pp. 166-175

LEE, A.L.Z. et al., 2013. Injectable Hydrogels from Triblock Copolymers of Vitamin E-Functionalized Polycarbonate and Poly(ethylene glycol) for Subcutaneous Delivery of Antibodies for Cancer Therapy. Advanced Functional Materials, , pp. n/a-n/a

NAHTA, R., 2012. Pharmacological strategies to overcome HER2 cross-talk and Trastuzumab resistance. Current medicinal chemistry, 19(7), pp. 1065-1075

http://www.fiercedrugdelivery.com/story/...2013-10-31 [Accessed 31 October 2013].