new herceptin targeted immunoliposomal drug being developed--works vs. herceptin res

[Lani]

istant cell lines in vitro (in the Petri dish). Very potent : concentration of drug needed to reduce tumor cell growth and viability using this liposome therapy is approximately 57,000-fold less than the concentration needed if drug is delivered extracellularly

Targeting Her-2+ Breast Cancer Cells with Bleomycin Immunoliposomes Linked to LLO

AbstractHi-Res PDF[2381 KB]PDF w/ Links[641 KB]
Max Kullberg, Kristine Mann, and Thomas J. Anchordoquy
Mol. Pharmaceutics, Just Accepted Manuscript
DOI: 10.1021/mp300049n
Publication Date (Web): May 23, 2012
Copyright © 2012 American Chemical Society

Abstract
Bleomycin is a membrane impermeable chemotherapeutic agent that is relatively innocuous extracellularly but highly cytotoxic when delivered directly to the cytoplasm. We report on the development of a liposome delivery system that targets Her-2 overexpressing breast cancer cells and breaches the endosomal barrier, delivering bleomycin to the cytoplasm. The liposomes are conjugated to the antibody trastuzumab, which results in specific binding and internalization of liposomes into Her-2 overexpressing cells. In addition, the liposomes are disulfide bonded to a pore-forming protein Listeriolysin O (LLO) which forms pores in the endosome and allows the liposomal cargo to pass into the cytoplasm. We demonstrate specific delivery to Her-2 positive MCF-7/Her18 cells relative to Her-2 negative MCF-7 cells using a fluorescent probe calcein within the immunoliposomes. When calcein is replaced by bleomycin, the liposomes effectively reduce viability of five different Her-2 overexpressing cell lines (BT-474. SKBR-3, MCF-7/Her18, HCC-1954 and MDA-453) while harming to a much lesser extent Her-2 negative breast cell lines (MCF-7 MCF-12a and MCF-10a). The liposomes also affect trastuzumab-resistant cells, reducing MDA-453 cell number by 97% compared to untreated cells. Importantly, the concentration of drug needed to reduce tumor cell growth and viability using this liposome therapy is approximately 57,000-fold less than the concentration needed if drug is delivered extracellularly, raising the possibility of increased therapeutic specificity with decreased side effects.

[Mandamoo]

This sounds really interesting! Do you know if this is close to trial in humans?

[Lani]

the fact it was published in an american chemical society journal makes me worry it might not be starting clinical trials too soon. Not everyone reads so widely in the literature, so this may get missed ... It depends if they get to give a paper or present a poster at a conference, have good connections to those who could develop it further etc.

Had Genentech done the work, I would think they might work on it as an alternative to TDM1 and things might move ahead faster.

If I see someone presenting on something similar @ ASCO I will bring it to their attention, so maybe they can collaborate and move things forward faster.

[StephN]

Thanks Lani -

ASCO is a place where thousands of researchers are present and do like to network to some extent. Many are looking for support to further what they have already come up with, so GO FOR IT "Sharp Eyes."