Antibodies Are The New Cancer Weapon

Antibody-based imaging* of a particularly aggressive form of breast cancer is undergoing clinical trials worldwide, but the path from trial to application is being hampered by a major obstacle: safety. Concerns stem from inefficient tumor targeting, which can result in accumulation in the bone marrow, liver and kidneys of the radioactive material necessary for the imaging. Recent efforts have focused on nanoscale delivery vehicles with immune components, but these vehicles are often still too large (20 nanometers or larger) for renal clearance after imaging.

Ulrich Wiesner, the Spencer T. Olin Professor of Engineering in materials science and engineering, in collaboration with Dr. Michelle Bradbury of Memorial Sloan Kettering Cancer Center (MSKCC) and Weill Cornell Medicine, has proposed a novel approach using ultrasmall silica nanoparticles – better known as “Cornell dots” (or C dots) – invented in his lab more than a dozen years ago. Their team – including researchers at pharmaceutical company MedImmune – have equipped the C dots with antibody fragments. Because the resulting conjugates are smaller than 8 nanometers, these C dots allow for renal clearance while achieving the specificity needed for efficient tumor targeting.

They report their discovery in in Nature Communications. Feng Chen, senior research scientist at MSKCC, and Kai Ma, postdoctoral researcher in the Wiesner lab, are co-lead authors. Wiesner said this research creates “a whole new runway” to employ antibody fragments for a number of diseases, cancer in particular, and for diagnostics as well as drug delivery – when combined in a single entity also known as “theranostics.”

A rendering of the Cornell prime dot (left) with an attached antibody fragment (center) binding to a HER2 cancer cell receptor (right). The dot and antibody attachment combined are less than 8 nanometers in diameter, the limit for renal clearance.

This is the first time we’ve worked with these antibody fragments,” Wiesner said, “thereby harnessing the power of antibodies in the fight against cancer.”

Cornell dots and their newer generation – termed “Cornell prime dots,” or simply C’ dots – have evolved since Wiesner and his group introduced them in 2005 and since, in collaboration with Bradbury, a first clinical trial deemed them safe for humans in 2014. Two years ago, the dots were shown to have the ability not only to detect cancer cells but to be self-therapeutic thereby actually killing them.

Cancer imaging is an umbrella term that covers the many approaches used to research and diagnose cancer. Originally used to diagnose and stage the disease, cancer imaging is now also used to assist with surgery and radiotherapy, to look for early responses to cancer therapies and to identify patients who are not responding to treatment.

Source: http://news.cornell.edu/

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