Cells of the innate immune system, such as macrophages, NK cells, neutrophils, eosinophils and particularly dendritic cells (DC), guide immune reactivity towards a protective antitumor response, according to the cytokines that these cells are specialized to produce. The immunological linking of the adaptive immune response and innate immune system is orchestrated by cytokines like GM-CSF, TNF, IL-12, IL-18 and IFN-γ that are produced by the cells of the innate immune system in response to physiological cues of “danger.” These so-called “danger-signals” include tissue inflammation and destruction as well as soluble and secreted components of bacterial or fungal species and factors ... Read more

There was an overwhelming belief that neurons were only produced during embryogenesis and perinatally in the mammalian central nervous system (CNS). The existence of neural stem cells in the adult brain was essentially denied until a decade ago. Only in recent years has the adult CNS been imagined to have the potential to regenerate after injury or disease. It is now evident that new neurons are generated in the mature brains of mice and primates. The sources are neural stem or progenitor cells which can self-renew and generate more specialized cell types in neural tissues. Another dogma which governed the ... Read more

Stem cells have enormous therapeutic potentials. As of today, however, they remain as a “loose cannon.”

Scientists and clinicians are attracted to stem cells’ potential to divide and differentiate. There are, however, numerous hurdles to cross in order for stem cells to have safe, reliable, and predictable therapeutic benefits. Chief among the hurdles are the difficulty in harnessing the stem cells to differentiate into the right kind of functional mature cells and behave like normal differentiated cells.

Drs. Tsai and McKay of National Institutes of Health reported recently that they discovered a novel protein, nucleostemin, that is found in both stem cells ... Read more

Transgenic animal models have been instrumental in the fields of experimental and applied biology. They serve as models to study many biological processes that would not be possible without them. Many transgenic disease models closely mimic human diseases that are as complex as diabetes, Alzheimer’s disease, cardiovascular diseases, etc.

The current widely used technique for producing transgenic animals is to microinject a transgene into the nucleus of a fertilized egg. By this method, the transgene is randomly inserted into the genome, if at all. When the fertilized egg starts to divide, it is implanted into the uterus of a ... Read more

The imagination of biotechnologists in using chip technology does not stop at the revolutionary DNA microarray. They have so far succeeded in putting onto slides proteins, antibodies, drug compounds, and living cells. Recently added to this list were tissue samples. A tissue microarray is a single slide containing a large number of tiny tissue sections. This technology not only dramatically speeds up the laborious immunochemistry research, but also has a direct impact on many clinical pathology tests by increasing their efficiency and accuracy.

Depending on the research need, a medium-density tissue microarray can be practically constructed in many labs. ... Read more

Antisense technology is based on a simple and beautiful concept: a short stretch of DNA, whose sequence is complementary to a specific mRNA of interest, binds to the target and induces its degradation or blocks its expression. Since the first application of antisense DNA on Rous sarcoma virus expression in 1978, numerous DNA oligos have undergone clinical trials. In over two decades of developing this technology, scientists have accumulated a lot of valuable information.

In order to avoid degradation, antisense DNA oligos have to be modified to increase their stability (see table on next page). However, structural modifications of ... Read more

Proteins show remarkable plasticity in their sequence composition and arrangement while preserving biological functions. This is made possible by the large number of amino acid units, often in the hundreds or thousands, that comprise the protein. The ability to change each and every amino acid in a protein drug has already contributed to significant clinical benefits: greater efficacy and less adverse effects by decreasing immunogenicity and functionally improved specificity. The native protein is optimized for its normal biological function. Scientists take the hint from nature and make it a therapeutic: a powerful force to perturb and correct a disease state.

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Name: Amevive.

Other Names: Alefacept.

Maker: Biogen Inc.

Disease Treated: Adult patients with moderate to severe plaque psoriasis.

Approval Status: Approved by the US FDA for marketing on January 31, 2003.

Chemical/Biological Nature: AMEVIVE is a fusion protein composed of the extracellular CD2-binding portion of the human leucocyte function antigen-3 (LFA-3, or called CD11a) linked to the Fc portion of a human IgG1 antibody. The molecular weight of AMEVIVE is 91.4 kD. It is generated by recombinant DNA technology using Chinese hamster ovarian cells.

Administration: 7.5mg once a week by intravenous injection or 15mg once a week by intramuscular injection. The recommended treatment regimen ... Read more

Other Names: D2E7, Adalimumab.

Maker: Abbott Laboratories.

Disease Treated: Adult moderate to severe cases of rheumatoid arthritis who have had an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs).

Approval Status: Approved by the US FDA for marketing on December 31, 2002.

Chemical/Biological Nature: HUMIRA is a recombinant all human IgG1 monoclonal antibody specific for human tumor necrosis factor alpha (TNF-α). Components responsible for the antibody’s specificity were discovered by phage display technology (Discovery Medicine, November 2002). The monoclonal antibody is composed of the human antibody heavy and light chain variable regions and human IgG1 constant region. HUMIRA has 1,330 amino acids and ... Read more

Other Names: Tositumomab and ¹³¹I-Tositumomab.

Makers: Corixa of Seattle, WA and GlaxoSmithKline of Philadelphia, PA.

Disease Treated: Non-Hodgkin’s B-cell lymphoma (NHL). There are currently about 300,000 cases of NHL in the United States, with more than 56,000 new cases predicted to have been diagnosed in 2002. The National Institute of Cancer estimates that approximately 140,000 people have low-grade NHL or transformed low-grade NHL, an aggressive, difficult-to-treat, and particularly deadly form of the disease for which BEXXAR is indicated. The American Cancer Society estimates that 24,400 people would die of non-Hodgkin’s lymphoma in the United States in 2002.

Chemical/Biological Nature: Unlabeled and ¹³¹I-labeled murine ... Read more