Photoimmunotherapy uses monoclonal antibody with near-infrared photosensitizer

This creative approach to cancer treatment relies on the greater tissue penetrance of infrared compared to visible light. Very well done!

 

National Cancer Institute

at the National Institutes of Health

Questions About Cancer? 1-800-4-CANCER

 
  • Posted: 11/07/2011

NIH researchers design a light therapy that targets and destroys cancer cells in mice:

NCI Press Release

Researchers have designed a light-based therapy that allows the selective destruction of tumor cells in mice without harming surrounding normal tissue. This method of cancer therapy could theoretically work against tumors in humans, such as those of the breast, lung, prostate, as well as cancer cells in the blood such as leukemias, say scientists from the National Cancer Institute (NCI), part of NIH. The study appeared online Nov. 06, 2011, in Nature Medicine.

Current photodynamic therapy is not specific for cancer cells, resulting in damage to surrounding normal tissue. Therefore, the researchers in this study set out to develop a light therapy that could more accurately target cancer cells while sparing a greater number of normal cells.

Image of a mouse with two implanted tumors (circles) that received the photoimmunotherapy (PIT) agent. One tumor was covered (white circle) but the other tumor (yellow circle) received a short course of harmless near infrared light. One day after exposure to the light, the treated tumor is dramatically smaller than the covered tumor demonstrating the effectiveness of PIT.This new type of treatment, called photoimmunotherapy, or PIT, uses light to rapidly and selectively kill cancer cells. To create their PIT, the scientists coupled a monoclonal antibody or MAb, which recognizes specific proteins on the surface of cancer cells, with a photosensitizer—a molecule that, when exposed to light of the appropriate wavelength (near-infrared), rapidly damages cells. The hope was that the combined photosensitizer/MAb would, by delivering the photosensitizer to cancer cells targeted by the MAb, selectively kill those cells after exposure to near-infrared light.

After evaluating a large number of photosensitizers, the scientists found that a near infrared fluorescent dye called IR700 had the most favorable chemical properties.

The scientists chemically linked IR700 to three different MAbs, including antibodies that target HER2, which is overexpressed by some breast cancers; EGFR, which is overexpressed by some lung, pancreatic, and colon cancers; and PSMA, which is overexpressed by prostate cancers. The researchers found that when cancer cells bound MAb-IR700 and were exposed to near-infrared light, the targeted cells rapidly died whereas cells lacking the ability to bind the complex were unharmed. When the complex was tried in mouse models of cancer, even a single dose of near-infrared light resulted in dramatic tumor shrinkage in mice that had been given MAb-IR700. Like visible light, infrared light has a range of wavelengths that range from red light to violet; near-infrared light is closest in wavelength to visible light.

Photoimmunotherapy using MAb-IR700, unlike conventional photosensitizers which can cause damage to healthy tissue, does not appear to harm normal cells. Whereas the light that is required to activate conventional photosensitizers can penetrate through only about 0.8 centimeters of tissue (about a third of an inch), the near-infrared light used to activate IR700 can penetrate tissue to a depth of several centimeters (One centimeter is .39 inch).

The study also found antibody doses required for diagnosis were significantly lower than those required for therapy. Nevertheless, after MAb-IR700 exposure, the targeted tumors decreased in size and eventually disappeared, suggesting a potential means of controlling cancers with far lower doses of MAb than are usually administered to cancer patients, say the scientists.  Because the MAb-IR700 compound also emits a small amount of light, it can be used to monitor therapy as well.

“The ability to join different MAbs to IR700 means that this technique might be used as a non-invasive guide to monitor the results of treatments,” said Hisataka Kobayashi, M.D., Ph.D., chief scientist in the Molecular Imaging Program at NCI’s Center for Cancer Research. “Although more testing will be needed, we believe this PIT method has the potential to replace some surgical, radiation, and chemotherapy treatments.”

 

# # #

 

Reference: M Mitsunaga et al. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Online Nature Medicine, Nov. 06, 2011, DOI: 10.1038/nm.2554.

 

 

 

Intelligent Fingerprints

A great example of two technologies finding an intersection to form a “marriage” or “sandhi,” to use the Sanskrit grammar term for a harmonious union between adjacent words:

“Drug testing device, hand-held, from the sweat contained in fingerprints
Posted on November 12, 2011 by Stone Hearth News

The world’s first prototype of a hand-held fingerprint drug testing device has been created by UK technology company Intelligent Fingerprinting.

The unique device detects drugs and other substances from the sweat contained in fingerprints and will enable mobile testing with instant results.

A spin-out of the University of East Anglia (UEA), Intelligent Fingerprinting Ltd is based in the NRP Innovation Centre at the Norwich Research Park. The company developed the prototype with eg technology – a product design, development and engineering consultancy based in Cambridge.

Paul Yates, business development manager at Intelligent Fingerprinting, said: “The launch of this prototype is a significant milestone. There has already been considerable worldwide interest in the use of the technology for testing within a wide range of applications, including criminal justice forensic science, homeland security, and institutional testing such as prisons and workplaces. But the ability of a hand-held device to carry out testing in-situ brings a whole new range of benefits and opportunities.”

The device will enable testing of fingerprints for illegal drugs and other substances using disposable cartridges. The samples are quick and easy to collect and do not require specialist handling or biohazard precautions. Because of the imaging of the fingerprint, they have an in-built watertight chain of evidence continuity and are almost impossible to cheat.

The potential uses for the device are wide ranging and cover testing individuals in the workplace – especially in safety critical industries where there is a need to judge whether someone is ‘fit for duty’ – through to screening drivers at the roadside for drug-driving impairment.

David Russell, CTO of Intelligent Fingerprinting and Professor of Chemistry at UEA’s School of Chemistry, said: “The development of the Intelligent Fingerprinting hand-held testing device has been a technological success. Working closely with eg technology we have been able to design a device that carries out the full analysis and imaging of a fingerprint in only a few minutes. The first prototype will be able to test individuals for drugs of abuse but we will be working to widen the range of substances to include other drugs and health markers that are found in fingerprints.”

The prototype is scheduled to go into full production in 2012 and the team will work with customers to develop new applications.

Danny Godfrey, director of eg technology, said: “Intelligent Fingerprinting’s core intellectual property is fascinating, offering a unique, robust way of linking a test result to the individual. Designing a device to automate their well-defined laboratory process has required input from all of our skill groups – microfluidics, optics, electronics, software, industrial and mechanical design. The release of the prototype is a major milestone towards the unveiling of the production device next year and we’re delighted to be part of such an exciting development.” “

Interesting article on nanomedicine implications for safety and pharmacovigilance from Global Forum

This article by A. Michael Bloh in the October issue of DIA’s Global Forum is summed up by it’s title:
“Nanotechnology and Nanomedicine: Implications for Drug Safety, Pharmacovigilance, and Risk Management.”

The risks to biotechnologists in formulating nanomedicines and to the environment through nanoparticle contamination are also reviewed. This is an excellent introduction or update to the subject.

Nanotechnology and Nanomedicine Implications for Drug Safety, Pharmacovigilance, and Risk Management_globalforum20111011-1317946860000e19c97bdf0-pp