LGND's neighbor, IDPH, is getting some good press for their monoclonal:
by Stephen Hart
ABCNEWS.com
For more than 20 years, scientists have sought a
way to use the body's own disease-fighting
chemicals as medicine, especially against cancer.
In late November, they passed a major milestone in their
quest, when the Food and Drug Administration approved a
new drug called Rituxan for the treatment of one type of
cancer.
Generically known as rituximab, Rituxan is the first cancer
therapy based on naturally occurring immune
proteins-so-called monoclonal antibodies. In an ironic twist,
the drug acts specifically on non-Hodgkin's lymphoma, a
cancer affecting the very cells that produce antibodies, the
white blood cells called B cells that are found in lymph nodes.
In non-Hodgkin's lymphoma, B cells can become
malignant and form tumors in lymph nodes. Because these
cells circulate in the blood, non-Hodgkin's lymphoma rarely
occurs as a single tumor in one lymph node, and often affects
a number of nodes and the spleen or liver.
In the United States, about 240,000 people have
non-Hodgkin's lymphoma; most are over age 50. Some
non-Hodgkin's lymphomas grow quickly, killing patients
within weeks. Rituxan has been tested only on people with a
slow-growing form of the cancer.
Designer Tumor Fighters
The search for a monoclonal antibody cancer treatment
began in the 1970s. The researchers working on the idea
knew that healthy B cells produce proteins called antibodies
in response to a foreign substance, or antigen, entering the
blood. They also knew that when a single B cell encounters
an antigen, it multiplies to form a clone of itself.
Essentially, these B cell clones work as antibody factories
distributed throughout the body. They react only with the one
antigen, sticking to it whether it occurs in the blood or on the
surface of a cell.
Scientists grew B-cell clones specific to a certain antigen
by injecting tumor cells into mice, who produced antibodies
to those specific cells. The lofty goal of this process was to
produce designer medicines -called monoclonal
antibodies-for many diseases.
Practical Problems
It was a great idea, says Brian Link, a specialist in
monoclonal antibody therapy at the University of Iowa and a
member of the team that investigated Rituxan. "It was initially
thought then, that's fine, that'll be easy, all we need to do is
make a whole host of monoclonal antibodies against these
various cancer targets and away we'll go," says Link.
But because the early experimental monoclonal antibodies
came from mice, human patients' immune systems attacked
the mouse antibodies as foreign.
Still, says Link, researchers "thought that the problems
could be overcome if they could figure out a way to convert
most of the antibody molecule to a human framework. That
line of inquiry eventually led to Rituxan.
"The vast majority of Rituxan," Link explains, "is a human
antibody framework with just small amounts of mouse protein
cloned in."
The Progress of Cancer Treatment
Surgery
The earliest record of surgical cancer treatment dates to the
time of Aristotle, some 300 years B.C. Effective cancer
surgery-beginning with mastectomies-began in the late
1800s after the advent of anesthesia. Lasers and other
high-tech tools now allow surgeons to remove cancers while
sparing a breast or limb, for example.
Radiation
Radiation treatment debuted soon after Wilhelm Konrad
Roentgen discovered X-rays in 1898. X-rays penetrate tissue
poorly, however, burning skin before killing deep cancer
cells. But modern radiation uses tightly focused, high-energy
beams to precisely target tumors deep in the body.
Chemotherapy
German physician/chemist Paul Ehrlich introduced the first
chemical therapy-for syphilis-in 1908, coining the term
"magic bullet." Cancer chemo began in the 1940s. Today
some three dozen chemicals are used as anticancer agents.
None are magic bullets; they all attack any growing cells,
cancerous or healthy.
Immunotherapy
Experimental immunotherapy debuted in the early 1970s.
Technically a form of chemotherapy, immunotherapy targets
specific types of cells, rather than all growing cells. Rituxan
is the first such agent approved by the FDA for cancer.
Direct Attack
By the 1980s, researchers had figured out how to fool a
patient's immune system into accepting a monoclonal
antibody, using genetic engineering. But they were still only
part of the way to an effective therapy, says David G.
Maloney of the Fred Hutchinson Cancer Research Center
and the University of Washington in Seattle.
Maloney's involvement began with the first patient to
receive Rituxan in the earliest trials.
"In those days,"he says, "we were actually making custom
antibodies for each patient's tumor. It was just really not
practical." The key to a practical cancer therapy came with
the discovery of a chemical called CD-20, which is found on
most B cells. CD-20 seems to play a role in B-cell growth,
reproduction and, possibly, normal cell death, but how-or
if-the chemical affects cancer treatment remains unknown.
Also still unclear is how Rituxan actually works.
Researchers think it flags both malignant and normal B cells
for destruction, thus triggering the body's immune system to
attack with killer cells and/or cell-bursting chemicals. And in
the laboratory, at least, Rituxan has also been shown to act
directly on cancer cells, causing them to stop growing and
eventually shrivel up and die. "So for a number of reasons,"
says Maloney, "this has turned out to be a spectacular new
treatment."
Not a Cancer Cure
Even with the new therapy, however, researchers caution that
non-Hodgkin's lymphoma remains incurable, and patients
receiving any kind of treatment may suffer recurrences of their
tumors. A four-week course of Rituxan wipes out all of a
patient's B cells, but a normal B-cell population returns after
several months.
Rituxan appears to stave off malignant growth up to 11
months, however, and in clinical trials patients suffered few
side serious effects.
"Certainly as a single agent Rituxan does have value," says
Maloney. "But I think its real value will be in using it earlier in
the course of the disease, combined with or following other
standard chemotherapies." Even though it's not a cure, for
many patients with non-Hodgkin's lymphoma, Rituxan
represents a major step in quality of life. |
