Nov 9, 2007

Targeted cancer therapy involves delivery of a tumouricidal agent - be
it heat, radiation, cytotoxic drugs or antibodies - directly to the
tumour cells in order to effect selective cancer destruction with
minimal damage to healthy tissue. In research published last week, two
innovative schemes for performing targeted treatment are proposed: RF-
induced heating of nanotubes and UV activation of therapeutic
antibodies.

First up, a team led by scientists at the M D Anderson Cancer Center
(Houston, TX) and Rice University (Houston, TX) has demonstrated that
cancer cells treated with carbon nanotubes can be destroyed by
exposure to radio waves (Cancer 2007 doi: 10.1002/cncr.23155).

Carbon nanotubes - hollow cylinders of pure carbon - release heat when
exposed to a radiofrequency (RF) field. If the nanotubes are localized
within tumours, this thermal effect will destroy the cancer cells.
Without such a target, the radio waves pass harmlessly through the
body.

In preclinical experiments, the researchers injected a solution of
single-walled carbon nanotubes directly into liver tumours in four
rabbits. The rabbits were then exposed to a 13.56 MHz RF field for two
minutes, resulting in complete destruction of their tumours. No side
effects were noted, although some healthy liver tissue within 2-5 mm
of the tumours sustained heat damage due to nanotube leakage. Control
tumours, which were treated only by RF exposure or only by nanotube
injection, were unaffected.

"These are promising, even exciting, preclinical results in this
liver-
cancer model," said Steven Curley, professor in M D Anderson's
department of surgical oncology. "Our next step is to look at ways to
more precisely target the nanotubes so they attach to, and are taken
up by, cancer cells while avoiding normal tissue."

Research is now underway to bind the nanotubes to antibodies, peptides
or other agents that target molecules expressed on cancer cells, which
would allow sole targeting of the nanotubes to the tumour cells. As RF
fields penetrate deep into tissue, once this targeting is achieved, it
will be possible to heat up nanotubes anywhere within the body. Curley
estimates that a clinical trial is at least three to four years away.

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Ultraviolet action
Meanwhile, scientists at Newcastle University in the UK have developed
a cancer therapy that uses UV light to activate antibodies, which then
specifically attack tumours. Therapeutic antibodies have long been
recognised as having excellent potential but getting them to
efficiently target tumour cells has proved tricky.

To address this problem, the Newcastle researchers have developed a
way to "cloak" the antibodies by coating their surface with a photo-
cleavable organic oil, which prevents the antibody from reacting
within the body. The cloaked antibodies can be reactivated by
irradiation with UV-A light (ChemMedChem 2007 doi: 10.1002/cmdc.
200700200).

Once reactivated, the antibodies bind to T-cells, the body's own
defence system, and trigger them to target the surrounding tissue. The
researchers also demonstrated that activating the cloaked antibodies
near to a tumour will destroy it - effectively enabling antibody
targeting by simply shining UV light at the relevant area of the body
(ChemMedChem 2007 doi: 10.1002/cmdc.200700116).

"A patient coming in for treatment of bladder cancer would receive an
injection of the cloaked antibodies," explained Colin Self, professor
of clinical biochemistry. "She would sit in the waiting room for an
hour and then come back in for treatment by light. Just a few minutes
of the light therapy directed at the region of the tumour would
activate the T-cells causing her body's own immune system to attack
the tumour."

Self cited one example in which this treatment is used on patients
undergoing surgery for prostate cancer. "After the surgeon has removed
the bulk of a tumour, the patient could then be injected with
bispecific antibodies and a light shone at the affected area," he
explained. "This would target the patient's own immune system to the
tumour site."

BioTransformations, the company set up by Self to develop this
technology, is looking to begin clinical trials on patients with
secondary skin cancers in early 2008.
About the author

Tami Freeman is science editor on medicalphysicsweb.

http://medicalphysicsweb.org/cws/article/research/31766