In August of 2018, Novartis's first CART therapy was approved for marketing in the United States. While people are excited about new anti-cancer therapies, their prices have also sparked a huge controversy. Obviously, although Novartis only charges patients who have been treated for one month after receiving Kymriad treatment, the one-round price of US$475,000 still discouraged a large number of patients.



However, many professionals are not surprised by the pricing of this “one-time treatment”, and even said it is not high. For example, researchers at the National Institute of Health and Nursing (NICE) say that the value of CAR-T therapy can be as high as £500,000. If used as a transition procedure before bone marrow transplant, CAR-T is expected to provide patients with an average of 8.82 quality-adjusted life years (QALY), compared to 1.36 for current care. If you try to cure the disease, CAR-T will provide 11.18 QALY, which is much higher than the 1.11 QALY given according to traditional care standards. But in any case, even if it is "value for money", it will still not be useful for the patient if they can’t get treated.

Is the cost of T-cell therapy impossible to reduce?

Not true! After all, life experience tells us that new things are always the most expensive at initial time, and cost decreases with the improvement of technology and processes. For example, genome-wide testing needs billions of dollars at the beginning of this century, but in less than two decades, that number has fallen below one ten-thousandth. Today, the price of a CART treatment at Novartis can measure the whole genome hundreds of times.

So where does T cell therapy have room to reduce costs? let's look at it together!

Universal CAR-T
At present, Novartis's CART therapy is not "universal", but is carried out using autologous CART. Autologous CART has the advantages of good effect and immune exclusion, but its “personalized” preparation determines the complexity of the process and greatly increases the price. We all know that “mass production” can greatly reduce costs, so if allogeneic CART therapy, or “universal”, can overcome adverse effects such as graft-versus-host disease (GVHD), it will definitely reduce the cost of therapy.

As early as 2015, Cellectis had a successful case of allogeneic CAR-T therapy based on gene editing technology. It is expected that a donor of Cellectis's allogeneic CAR-T therapy can provide treatment for up to 500 patients, so the cost will be reduced to about 1/5 of Novartis. Just in July of this year, allogeneic CART cell products from Celyad were approved by the FDA in the United States, the first non-genetically edited allogeneic CART clinical project. In the future, it is believed that allogeneic CART therapy can promote the industrialization of T cell therapy and significantly reduce production costs.

Gene editing technology
In addition to a small number of non-genetically edited CAR-T therapies, autologous T-cell therapies require the isolation of immune T cells from patients, and then use gene editing techniques to add T cells to an element that recognizes specific tumor cells, making T cells A chimeric antibody that kills such tumor cells. This also means that genetic editing technology, as one of the cost links, also has a certain price reduction space. In particular, CRISPR, which was first reported in 2012, has been widely recognized by the academic community. A number of CRISPR technology research and development companies have partnered with major pharmaceutical companies to improve the safety and effectiveness of CART and TCRT immunotherapy.

Cold Chain Logistics
Can you imagine that so important cells to the patient were delivered by logistic companies? Of course not. Cell storage conditions are far more demanding than ordinary items, not to mention life-saving cells that cannot be lost. Therefore, cell therapy companies are basically building their own transportation systems to ensure cell viability. Obviously, this is another high but potentially avoidable cost. Compared with each company's own establishment of a cold chain transportation system, if there is a professional "medical express" to be unified and responsible, it will undoubtedly be able to significantly reduce the burden on cell therapy companies.

In fact, some people in the United States have turned their attention to this field. UPS has set up a health management division. The person in charge believes that logistics transportation is one of the key factors in the industrialization of CAR-T, which can directly affect the clinical response and efficacy.

Delicate segmentation
If ten people want to do a hundred pants, is it that each person makes ten pieces faster, or divide the process of "making pants" into ten processes, and the assembly line operation? Obviously, the latter is faster. And if you can rely on the help of the machine, then the speed will be even faster! The concept of “pipeline” and “automation” has always been a tool to improve efficiency, even in the pharmaceutical industry. Nowadays, more and more large enterprises are outsourcing research and development links such as pre-clinical research to enterprises that specialize in a specific link, and this trend is getting worse. The increasingly clear segmentation of labor has also allowed the entire industry to see sufficient room for efficiency improvement. As efficiency improves, the cost naturally decreases.

In addition, more and more detailed parts will inevitably spur the company to continuously upgrade the level of research and development and production processes. For example, under the current experimental method, it takes several weeks to prepare T cells for patients, and it is difficult to measure the effects of engineered cells. However, if a new synthetic protein tag called Strep-tagII is used, the T cell production rate can be increased, and the culture time can be greatly reduced (it takes 14-20 days, and can be shortened to 5 days or even shorter after the improvement), and The purity of anti-cancer CAR-T cells can be increased to 95% by inserting a Strep tag into the extracellular domain of the T cell receptor, whereas without the Strep tag, the purity of CAR-T cells is typically less than 50%. High purity, short time means a significantly increased yield, which also means that cost reduction is possible.