The new magic ball against cancer

Düsseldorf Since the outbreak of the pandemic, about 140,000 people in Germany have died from or with coronavirus and more than 500,000 people are likely to have lost the battle against cancer in the same period. Such data and relationships remind us that the challenges facing medicine in the 21st century still far outweigh the cure for infectious diseases.

You can also see it with the leading player in Covid vaccine development, Biontech SE. As a result, the Mainz-based biotechnology company wants to use the coronavirus’s success above all else to further its oncology research, said Biontech founder and CEO Ugur Sahin at Handelsblatt. The mRNA technology that has made the Covid vaccine so successful is also intended to create new cancer treatment options.

Biontech’s strategy and ambition are exemplary in an explosion of innovation in cancer treatment. It is already the largest source of income for the pharmaceutical industry and at the same time the most important field of research. Since 2011, the number of new clinical trials in the field each year has increased by almost 90 percent to more than 2,300 last year, and the number of potential anticancer drugs in clinical development has more than doubled to nearly 2,200 over the period, according to the U.S. Iqvia, the world ‘s leading pharmaceutical market researcher and service provider in clinical development.

Wide range of treatments

The risks and failure rates are still very high. Only a fraction of the projects prove to be successful. This is mainly due to the diversity and complexity of cancer diseases. Nevertheless, the number of new funds is increasing. According to Iqvia, 104 new cancer treatments have been approved worldwide in the last five years, twice as many as in the previous five years.

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The flood of new products has already significantly expanded the range of treatments in recent years. By the 1990s, the pharmaceutical industry had little more to offer than conventional chemotherapy – cytotoxins that kill cancer cells but also severely affect healthy tissue – there are now half a dozen other classes of active ingredients.

Targeted Drugs

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The starting point was drugs that specifically attack the molecular signals that lead to the overgrowth of cancer cells. Genetically modified antibodies in particular have thus achieved a prominent role in the treatment of cancer. These are complex protein molecules (proteins) that can attach to other substances in a very precise way and are therefore also used by the immune system to fight infections. The main pioneer was the breast cancer drug Herceptin, which targets the HER2 receptor.

immunotherapies

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At the beginning of the last decade, pharmaceutical researchers ushered in the era of immunotherapy for cancer. For the first time – also with antibodies – it was possible to block mechanisms by which cancer cells create molecular barriers against the body’s own immune system and thus protect themselves from defense cells.

Especially in skin cancer and lung cancer, but also in various other types of cancer, these so-called checkpoint inhibitors (CPIs) have been able to limit and delay the growth of the tumor. The successes brought the top products in the category billions in sales and caused an explosion in the industry. Eight active ingredients have now been approved and more than 5,000 clinical trials have been performed in which established and new CPIs are tested.

>> Read also: What Ugur Sahin says about vaccine strategy and cancer treatment research in an interview

The newest active ingredient in the series, the anti-cancer drug Jemperli from the British pharmaceutical company GSK, came up with particularly impressive results in a small study of patients with colon cancer a few days ago. In all 16 patients treated, the tumors completely disappeared within a year.

Cell therapies are another variant of immunotherapy. In the laboratory, the cells of the patients’s immune system are equipped with artificial receptors that are oriented to the cancer cells, multiply and inject again into the patient. In some cancers of the blood and lymphatic system, such as acute lymphocytic leukemia (ALL), these so-called CAR T cell therapies have shown very high response rates. In addition to the five products already approved, dozens of other cell therapies are underway, including those of the German biotech companies Immatics, Medigene and T-Knife. Biontech is also working on improved cell therapies.

Modified Antibodies

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Modified antibodies that can bind to two different structures simultaneously offer additional opportunities for the activation of immune cells against cancer cells. Two such bispecific antibodies have now been approved and more than 130 are in clinical development, some in combination with cell therapies. Heidelberg-based Affimed, for example, is working to load natural killer cells with such specific antibodies into the laboratory so that the cells can then attach more and more to the patient’s cancer cells and destroy them.

Another strategy followed by pharmaceutical researchers is to try to use the precision of antibodies to deliver chemotherapy to the tumor in a more targeted way. Antibodies bind to a cytotoxin. More than 100 such antibody-drug conjugates are in clinical trials and a good dozen have already been approved. A few days ago, for example, the drug Enhertu, developed by Astra-Zeneca and Daiichi-Sankyo, caused a sensation, which in a study in patients with a specific form of breast cancer, reduced the risk of developing the disease by about 50 percent and increased the survival rate accordingly.

new technology

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Other emerging technologies are maturing in laboratory and clinical trials, including mRNA-based drugs and first-line cancer vaccines. The technology, which has now been discovered in vaccines, could extend and promote cancer treatment, mainly because of its adaptability. Both Biontech and US competitor Moderna are testing, among other things, mRNA vaccines that are tailored to individual mutations in tumors, that is, that are individualized for each patient.

Another idea is to stimulate cancer cells through mRNA to produce antibodies or other substances, which in turn act against cancer cell growth drivers.

But other new ideas could also expand the range of treatments. Pharmaceutical and biotechnology companies are pinning their hopes on the “protein breakdown” process, for example. The goal is to use intracellular systems to break down unnecessary molecules in a targeted way for drug therapies. Harmful proteins are labeled with specific molecules for the cell’s disposal system.

A whole range of companies are working on new types of antibodies or further improved and standardized cell therapies that no longer need to be produced individually for each patient.
Even if none of the many projects and procedures offer the prospect of a cure – overall, the chances of further advancing cancer treatment are better than ever.

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