Immune System: Nanodrug Targeting Breast Cancer Cells

08/13/2013
Photo: Hair

A human hair is 80,000 to 100,000 nanometers wide. Researchers nanoconjugate is estimated to be about 27 nanometers wide; © pan-
thermedia.net/Christian Colista

A unique nanoscale drug that can carry a variety of weapons and sneak into cancer cells to break them down from the inside has a new component: a protein that stimulates the immune system to attack HER2-positive breast cancer cells.

The research team developing the drug – led by scientists at Cedars-Sinai Medical Center – conducted the study in laboratory mice with implanted human breast cancer cells. Mice receiving the drug lived significantly longer than untreated counterparts and those receiving only certain components of the drug.

Unlike other drugs that target cancer cells from the outside, often injuring normal cells as a side effect, this therapy consists of multiple drugs chemically bonded to a "nanoplatform" that functions as a transport vehicle.

HER2-positive cancers – making up 25 to 30 percent of breast and ovarian cancers – tend to be more aggressive and less responsive to treatment than others because the overactive HER2 gene makes excessive amounts of a protein that promotes cancer growth. One commonly used drug, Herceptin (trastuzumab), often is effective for a while, but many tumors become resistant within the first year of treatment and the drug can injure normal organs it contacts.

But Herceptin is an antibody to the HER2 gene – it naturally seeks out this protein – so the research team used key parts of Herceptin to guide the nanodrug into HER2-positive cancer cells.

"We genetically prepared a new 'fusion gene' that consists of an immune-stimulating protein, interleukin-2, and a gene of Herceptin," said Dr. Julia Y. Ljubimova. "IL-2 activates a variety of immune cells but is not stable in blood plasma and does not home specifically to tumor cells. By attaching the new fusion antibody to the nanoplatform, we were able to deliver Herceptin directly to HER2-positive cancer cells, at the same time transporting IL-2 to the tumor site to stimulate the immune system. Attaching IL-2 to the platform helped stabilize the protein and allowed us to double the dosage that could be delivered to the tumor."

Ljubimova led the study with Dr. Manuel Penichet of the University of California, Los Angeles. Ljubimova said the UCLA collaborators developed the fusion gene, and Cedars-Sinai chemists Dr. Eggehard Holler performed the technically difficult task of attaching it to the nanoplatform.

The researchers also attached other components, such as molecules to block a protein (laminin-411) that cancer cells need to make new blood vessels for growth.

The nanodrug, Polycefin, is in an emerging class called nanobiopolymeric conjugates, nanoconjugates or nanobioconjugates. They are the latest evolution of molecular drugs designed to slow or stop cancers by blocking them in multiple ways. Polycefin is intended to slow their growth by entering cells and altering defined targets. The new version also stimulates the immune system to further weaken cancers. "We believe this is the first time a drug has been designed for nano-immunology anti-cancer treatment," Ljubimova said.

Nano researchers manipulate substances and materials at the atomic level, generally working with substances smaller than 100 nanometers. Cedars-Sinai's nanoconjugate is estimated to be about 27 nanometers wide. A human hair is 80 to 100 nanometers wide.

MEDICA.de; Source: Cedars-Sinai Medical Center