Cartier Jewelry - My Magic Charm In the realm of luxury jewelry, Cartier stands out as an iconic and enchanting brand. With a rich history spanning over 150 years, it has become synonymous with elegance, opulence, and timeless beauty. For me, owning a piece of Cartier jewelry is like having a magical charm that enhances my style and brings an air of sophistication to any outfit. One of the most captivating aspects of Cartier jewelry is its impeccable craftsmanship. Every piece is meticulously designed and meticulously crafted, with attention to detail that is unmatched in the industry. The artisans at Cartier blend traditional techniques with innovative ideas, resulting in exquisite pieces that are truly one-of-a-kind.
Therapeutic Proteins: Key Markets and Future Strategies is available from Datamonitor, priced at $4,600.
For example, SmithKline Beecham has Bexxar iodine 131 tositumomab conjugate in R D, while IDEC Pharmaceuticals is developing Zevalin ibritumomab tiuexetan. For example, Genentech s Rituxan Mabthera rituxumab has been very successful since its launch in 1997, particularly in patients with refractory non-Hodgkin s lymphoma, which is difficult to treat with traditional small molecule cancer therapies.
The artisans at Cartier blend traditional techniques with innovative ideas, resulting in exquisite pieces that are truly one-of-a-kind. From the intricate engravings to the delicate gemstone settings, each element is expertly executed, creating a masterpiece that is both visually stunning and structurally sound. But beyond its craftsmanship, Cartier jewelry holds a deeper significance.
Magic bullets hit the target
After decades of disappointment, antibodies are finally emerging as viable — if expensive — drugs. Trisha Gura finds biotech start-ups and pharmaceutical giants rushing to claim a piece of the action.
For more than a century, doctors have dreamt of using antibodies as 'magic bullets' to cure their patients. After all, these highly targeted proteins are among the immune system's key weapons. So if specific antibodies against proteins involved in disease could be produced in bulk, they should be ideal bespoke drugs.
The story so far has been a roller coaster of hope and disappointment. Despite advances in techniques for producing antibodies in the lab, the magic bullets have — until recently — performed poorly in the clinic. But thanks to developments in genetic engineering, cancer biology, immunology and genomics, antibodies might finally be on the brink of realizing their therapeutic potential. “Now everybody is going crazy to make monoclonals,” says Leonard Presta, director of protein and antibody technology at DNAX, a biotech company in Palo Alto, California.
Monoclonals are antibodies mass-produced in the lab to recognize an individual molecular target. To date, the US Food and Drug Administration (FDA) has approved 11 of them — the majority in the past four years — to treat cancer and transplant rejection and to combat autoimmune diseases such as rheumatoid arthritis (see table). At least 400 other monoclonal antibodies are in clinical trials worldwide.
Table 1 Antibodies in action: monoclonal therapies approved by the US Food and Drug AdministrationOf mice and men: researchers have produced drugs based on (from the top) mouse, chimaeric, humanized or human antibodies. All have the same basic structure (bottom). Credit: P. JONES & G. WINTER
Antibodies are Y-shaped proteins, consisting of four polypeptides — two identical light and two identical heavy chains (see diagram). The arms of the Y identify and bind to the antibody's specific molecular target, or antigen. If that happens, the portions of the heavy chains that extend into the stem of the Y alert and recruit the other components of the immune system to attack the structure to which the antibody is bound.
The therapeutic appeal of antibodies can be traced back more than a century, when mice were first investigated as a potential source. By injecting mice with infectious agents, scientists aimed to stimulate the production of antibodies targeted against the infection. They hoped that they could then treat people suffering from the same condition by injecting them with the rodents' blood sera. But these crude preparations were ineffective, and the sera sparked adverse immune reactions in some unfortunate patients.
In 1975, however, Georges Köhler and César Milstein of the UK Medical Research Council's Laboratory of Molecular Biology (LMB) in Cambridge raised hopes with their invention of hybridoma technology 1 , later honoured with a Nobel prize, which for the first time allowed researchers to mass-produce individual antibodies. By fusing antibody-producing cells from immunized mice with antibody-secreting mouse cells derived from a type of cancer called myeloma, they generated hybrid cell lines that could be cloned and cultured indefinitely. Injected into mice, these immortalized cells grew into tumours that could produce large amounts of monoclonal antibodies. Today, improved cell-culture techniques mean that large quantities of monoclonals can be made without the need to grow tumours in mice.
Mouse antibodies worked well in rodent models of disease 2 . But when doctors started injecting mouse monoclonals into human patients, problems emerged. The patients' immune systems quickly recognized the mouse antibodies as foreign proteins, and generated 'human anti-mouse antibodies' that cleared the mouse proteins from the bloodstream before they had chance to work. In rare cases, the result was a fatal allergic response 2 .
Less is more
Researchers also soon realized that mouse antibodies could not function normally in people, because the structure of the proteins is subtly wrong. Even if the arms of a mouse monoclonal did manage to capture its corresponding antigen, the antibody's heavy chains could not signal the human immune system to attack the bound target 3 .
Indeed, only one mouse antibody made it through clinical trials. This monoclonal, called Orthoclone OKT3, was approved in 1986 and is used to help prevent the rejection of transplanted organs. It works by targeting a glycoprotein on the surface of T cells in the immune system that would otherwise recognize the organ as foreign. In effect, Orthoclone OKT3, marketed by Johnson & Johnson, shuts down one arm of the immune system — which helps to explain why it does not get cleared from the bloodstream quickly.
At the time, making completely human monoclonals was impracticable, because there was no human myeloma cell line suitable for making hybridomas. So scientists turned to genetic engineering of both mouse antibody-producing cells and hybridomas, mixing and matching DNA from mouse and human antibody genes in an attempt to make antibodies that would not be rejected by the human immune system. In the first of these chimaeras, genes encoding mouse antibody arms were simply grafted onto the genes for human antibody stems, producing antibodies that were roughly 30% mouse, 70% human. These chimaeric antibodies could communicate with the human immune system 4 . But problems continued — in many cases, the chimaeras were still sufficiently 'mousey' to be attacked by the immune system 5 .
The breakthrough came in 1986, when Greg Winter's group at the LMB shaved the mouse component of chimaeric antibodies down to only 5–10% (ref. 6). Winter knew that three loops of amino acids within a part of each antibody arm called the variable region acted as the 'glue' to bind antibody to antigen. So he replaced everything but the genes for these loops with human sequences. The resulting 'humanized' mouse monoclonals seemed to evade the human immune system. “All of a sudden, it looked like maybe these things would become drugs,” says Nils Lonberg, senior vice-president and scientific director of Medarex, a biotech company in Princeton, New Jersey.
As chimaeric-antibody technology and Winter's refined technique transferred to the biotech industry, a healthy pipeline of monoclonals lined up for FDA approval. In 1994, Eli Lilly of Indianapolis gained permission to market the first chimaeric antibody, ReoPro, which lessens the risk of blood clots in patients with cardiovascular disease by targeting a receptor protein on the surface of platelets. And in 1997, Roche of Basel, Switzerland, won approval for the first humanized monoclonal antibody, Zenapax — which combats organ rejection by binding to and inhibiting a receptor on activated white blood cells, which would otherwise stimulate tissue rejection.
The plethora of potential targets being identified by companies working in the fields of genomics and proteomics should fill the pipeline further. But so far, the main focus has been cancer, where a concentrated research effort has already identified many targets.
Solid start
Cooking up a storm: Genentech's new antibody production plant in Vacaville, California. Credit: GENENTECH
After first going after leukaemia and lymphomas, with some success, companies have moved onto solid tumours, which are generally harder to treat. Herceptin, marketed by Genentech of South San Francisco, targets and blocks a growth receptor on the surface of breast cancer cells. In a trial of 469 women with late-stage breast cancer who tested positive for the receptor, a combination of Herceptin and standard chemotherapy caused greater tumour shrinkage and extended the patients' lives by an average of five months, compared with chemotherapy alone 7 . That, in the world of oncology, is considered a success. “Any incremental therapy, we embrace,” says cancer researcher Rakesh Jain of the Massachusetts General Hospital in Boston.
The effectiveness of monoclonals against cancer might be improved by attaching toxins or radionuclides to the antibodies, to deliver a knockout punch to the targeted cells. In February, for instance, IDEC Pharmaceuticals of San Diego received approval for Zevalin, a radioantibody for use against non-Hodgkin's lymphoma. And some researchers are advocating the use of cocktails of monoclonal antibodies that will simultaneously target different molecules in multiple cell-signalling pathways. Jain has tried to do just that by testing Herceptin with another antibody, also made by Genentech, that inhibits the formation of blood vessels — needed to supply a growing tumour with oxygen and nutrients.
Intriguingly, Jain's team reported in March that Herceptin alone may do more than simply shut down the cancer cells' growth signal — it might also discourage the growth of blood vessels 8 . To some experts, findings such as these suggest that antibodies may have much broader applications than just inhibiting the function of particular proteins, or labelling them for attack by the human immune system. “You've got to think about antibodies as agents that change the biology of the cell,” says Lee Nadler, senior vice-president of experimental medicine at the Dana-Farber Cancer Institute in Boston.
In that vein, Nadler wonders if antibodies might be used to help boost the effects of chemotherapy or to sensitize cells to radiation. Monoclonals are also being explored for their potential to bind to a receptor and activate it.
In parallel with the clinical developments, techniques for producing and selecting antibodies have also been advancing, allowing the generation of completely human monoclonals. A technology called phage display, for instance, allows researchers to build libraries of human antibody genes and incorporate them into bacteriophages, viruses that infect bacteria. The phages reproduce in cultures of Escherichia coli, and researchers can fish out any desired antibody from the resulting phage 'soup' using the appropriate target antigen tethered to a surface 9 .
Human behaviour
Meanwhile, Medarex and another biotech company, Abgenix of Fremont, California, are working with mice engineered to have immune systems that are human, as far as their production of antibodies is concerned. Scientists first knocked out the rodents' ability to produce mouse antibodies by deleting regions of the rodents' heavy- and light-chain genes, and then added the equivalent human genes 10,11 . Now researchers just need to inject the rodents with the antigen of choice and the animals churn out completely human antibodies. “The beauty is that the mouse does everything for you,” says Geoff Davis, chief scientific officer at Abgenix.
At the same time, researchers have not given up on making human hybridomas. Abraham Karpas of the University of Cambridge, UK, has spent years patiently cultivating a human myeloma cell line that can withstand fusion with other antibody-producing cells and still grow properly. He reported success last year 12 . And in unpublished findings, Michael Neuberger at the LMB has come up with a way to speed up the generation of new antibodies using a line of antibody-producing cells that mutates its genes faster than normal.
But despite the current wave of enthusiasm, some problems remain. Investment in the antibody business recently took a hit as biotech company ImClone Systems of New York came under fire for inadequacies in its application to market a promising antitumour antibody (see 'Box 1 Giving antibodies a bad name'). But the biggest issue is cost. Although antibodies require much less investment in initial research and development than conventional small-molecule drugs, they are hugely expensive to manufacture.
This stems from the cost of scaling up antibody production to meet clinical demand. The proteins are usually generated by cell cultures in bioreactors that have a capacity of 40,000 litres or more. By the time the cells are nurtured, isolated and the antibodies they produce are purified, the cost can run as high as US$1,000 per gram — compared with $5 per gram for typical small molecules produced by chemical synthesis.
In addition, building a 100,000-litre facility, such as the one just completed by Genentech in Vacaville, California, can take five years and cost $400 million. “There is this tension that as more and more antibodies come on line, there is a real problem with making enough,” says Presta, who used to work for Genentech.
Right now, researchers are concentrating on trying to improve the efficiency of antibody production in cell culture. But they hope eventually to move to streamlined cell-free systems — a step that would surely place antibodies in the clinical mainstream. “We have a long way to go before the story is finished,” says Winter.
Box 1: Giving antibodies a bad name
Encouraging results from clinical trials of antitumour monoclonal antibodies have done much to boost stock-market and scientific excitement. But the good work was nearly undone by the story of Erbitux, a drug developed by ImClone Systems of New York.
Erbitux is a monoclonal targeted against the epidermal growth factor receptor, found on about a third of solid tumours. Early studies of patients with colon cancer and tumours of the head and neck yielded such promising results that, in February last year, the US Food and Drug Administration (FDA) granted ImClone fast-track status for Erbitux. All that remained were further controlled, randomized trials. “We work very closely with the FDA,” said Harlan Waksal, then chief operating officer of ImClone, last October. “They are our God.”
But within two months, Waksal and his brother Samuel, then ImClone's chief executive, had provoked their deity's ire by rushing the trials. According to David Milroy, an analyst with the consultants Wood Mackenzie in Edinburgh, UK, the FDA first grew concerned about an apparent discrepancy that suggested colorectal patients on whom other treatments had failed were, in fact, responding to a standard chemotherapy agent. The agency asked for data confirming that the patients had indeed lost their ability to respond to chemotherapy. ImClone was unable to provide this, and could only supply complete records for three of 17 patients who had died of cancer. Researchers in the field add that the trials lacked proper randomization and appropriate controls. Indeed, experts accuse the Waksals of letting stunts such as hiring rock group the Doobie Brothers to perform at the American Society of Clinical Oncology meeting in San Francisco in May last year take priority over sound science. “ImClone is an embarrassment to those trying to do good research,” says Lee Nadler, senior vice-president of experimental medicine at the Dana-Farber Cancer Institute in Boston.
For ImClone and others, the embarrassment has proved costly. The company is now facing investigation by the US Congress, the Department of Justice, and the Securities and Exchange Commission. Its stock fell from nearly $74 per share in early December to a low of $9.90 last month — and the ripples have spread. “Biotech in general and antibody companies in specific took a big hit,” says Geoff Davis, chief scientific officer of Abgenix, an antibody company in Fremont, California.
The irony is that most industry sources believe Erbitux to be an effective drug. But rather than relying on ImClone's data, Merck KGaA of Darmstadt, Germany, which owns the rights to develop and market Erbitux in Europe, and ImClone's US partner Bristol-Myers Squibb are now running fresh clinical trials.
Each collection tells a story, embodying an emotion or a cultural reference. Whether it's the iconic Love Bracelet symbolizing eternal love, the delicate Panthère de Cartier collection capturing the graceful strength of a panther, or the vibrant and playful Juste un Clou line celebrating the rebellious spirit, Cartier jewelry holds a special meaning for its admirers. Wearing Cartier jewelry makes me feel like I am carrying a piece of history and tradition with me. It is a reminder of the elegance and refinement that transcends time and trends. The iconic designs, such as the Cartier Trinity ring with its three intertwining bands, the Tank watch with its clean lines and geometric shape, or the Ballon Bleu de Cartier with its distinctive blue sapphire crown, have become synonymous with luxury and sophistication. Beyond its beauty and symbolism, Cartier jewelry is also a wise investment. Known for its value retention and rarity, it is treasured by collectors around the world. Cartier's reputation for quality and craftsmanship ensures that each piece not only withstands the test of time but also appreciates in value over the years. Owning a Cartier piece is like having a little piece of history and art that can be passed down through generations. In conclusion, Cartier jewelry holds a special place in the hearts of many, including mine. Its timeless beauty, impeccable craftsmanship, symbolic meaning, and investment value make it a truly magical charm. Whether worn for a special occasion or cherished as a family heirloom, Cartier jewelry is a treasure that brings joy and enchantment to its wearer..
Reviews for "The magical journey of Cartier jewelry: From conception to creation"
1. Emily - 2 stars - I was really excited to purchase the Cartier jewelry my magic charm, but when it arrived, I was very disappointed. The charm itself was smaller than I expected, and the quality was not up to par. The chain was flimsy and broke after just a few wears. I was also underwhelmed by the design, as it lacked the elegance I associate with Cartier. Overall, I regret my purchase and would not recommend this product.
2. Michael - 1 star - I have been a fan of Cartier jewelry for years, but the my magic charm completely missed the mark for me. The charm itself looked cheap and poorly made, and the chain was too short and uncomfortable to wear. The clasp was also difficult to use, making it a hassle to put on and take off. I expected much better quality from a brand like Cartier, and I am extremely disappointed in this product.
3. Sarah - 2 stars - I bought the Cartier jewelry my magic charm as a birthday gift for my sister, but she ended up being disappointed with it. The charm looked much different in person than it did in the pictures, and the stones were not as vibrant or sparkly as we had hoped. The chain also broke within a week of wearing it, which was very disappointing. My sister had to return it and we ended up getting her a different piece of jewelry instead. I expected better quality from Cartier and would not recommend this charm.