The first cell therapy product is on the market, and there is hope for "incurable" cancer

Audit expert: Zhang Jianwei

Deputy Chief Physician, Department of Oncology, Seventh Medical Center, PLA General Hospital

Not long ago, the first cell therapy product approved by China was launched on the market.

On June 22, China's National Medical Products Administration (NMPA) issued the latest public notice, approving the listing of Akilencel Injection (trade name: Yikaida) applied by Fosun Kite Biotech Co., Ltd. On the evening of June 28, a drug sales order suspected to be Fosun Kite Akilencel Injection circulated online, which showed that the retail price of Akilencel Injection was 1.2 million yuan per bag (about 68ml).

This piece of news has undoubtedly once again put cell therapy on the forefront of public opinion. First, there are patients' lives at stake, and then there are high prices. What exactly is cell therapy, and is it a trustworthy treatment method? How to distinguish pseudoscience from real progress from the dazzling information is worth discussing.

1

Classification of cell therapy

Cell therapy refers to a therapy that uses allogeneic (including xenogeneic and homologous) or autologous cells, which are processed in vitro and then transplanted into the human body for the purpose of treatment, diagnosis or prevention. It can be understood that cell therapy is a therapy that processes living cells from other people (or animals) or oneself and then transplants them into the human body.

Principles of cell therapy Source: bioscience.lonza.com

Cell therapy can be divided into stem cell therapy and differentiated or mature cell therapy based on the type of cells used. The only widely used stem cell therapy is hematopoietic stem cell transplantation, usually in the form of bone marrow transplantation, but the cells can also come from umbilical cord blood. There are currently many studies trying to develop various sources of stem cells and apply stem cell therapy to neurodegenerative diseases, such as Alzheimer's disease, as well as diseases such as diabetes and heart disease. However, due to ethical issues, research in this area has been controversial.

As for mature cell therapies, immune cell therapies are currently progressing at the fastest pace, among which the most popular is the immune cell therapy used to treat cancer.

Immune cells can be further divided into T cells, B cells, dendritic cells (DC), natural killer cells (NK), etc.

The DC-CIK therapy used by Wei Zexi a few years ago, namely dendritic cell-cytokine-induced killer cell therapy, is an immune cell therapy. Due to its unclear effect, no DC-CIK therapy has been approved for marketing. The unconventional therapy criticized by Dr. Zhang Yu earlier this year was NKT therapy. Similar to DC-CIK therapy, NKT uses a special T cell subset that has the characteristics of both NK cells and T cells. It is still an immune cell in nature, and no products are available on the market at home or abroad. The recently launched Fosun Kite Akilencel injection belongs to CAR-T therapy, which is the sixth CAR-T therapy in the world. So why is CAR-T therapy so popular?

2

CAR-T therapy

The full name of CAR-T therapy is chimeric antigen receptor T cell immunotherapy.

At present, drug regulatory authorities in many countries, including the US FDA, have approved more than 300 CAR-T cell therapy clinical trial projects. At the same time, some CAR-T cell therapies have been put on the market. The principle of CAR-T is to first collect T cells from the patient's blood, and then genetically engineer the T cells to produce proteins that can recognize tumor cell antigens. This modified molecule that can recognize tumor cell antigens is called a chimeric antigen receptor (CAR). T cells expressing CAR can recognize and bind to tumor antigens, and then attack tumor cells. When the modified T cells are injected into the patient's body, the patient's tumor cells will be attacked by the T cells.

So why are the newly launched CAR-T therapy drugs sold at such high prices? Here we would like to introduce another classification method of cell therapy, which is also commonly used in recent years.

CAR-T cell therapy and other cell therapies

Source: cn-healthcare.com

According to the source of the cells used for treatment, cells from the patient's own body are called autologous cells, while off-the-shelf cells can come from other people, or simply be induced from stem cells. The CAR-T therapies currently on the market are all derived from autologous cells, which are often expensive.

First, non-specific T cells are isolated from the patient, modified according to the patient's tumor cell type and characteristics, and then infused back into the patient. This process is usually complicated and takes 2-5 weeks. Most patients need radiotherapy or chemotherapy before receiving CAR-T cell therapy to reduce the incidence of rejection. Therefore, the patient may not have functional T cells in his body, which may lead to a longer production cycle of autologous CAR-T cells.

In addition, as a living cell drug, the preparation process has extremely high requirements for environmental cleanliness. Each patient is an independent batch, and each batch of products needs to strictly control the production environment and process and undergo comprehensive testing. The production and transportation costs are very high. Therefore, autologous CAR-T therapy is a completely personalized treatment method, and the high price is expected.

3

Cell therapy has a promising future

The approval of autologous cell therapy for marketing is undoubtedly good news. Even though the average person cannot afford the cost now, it still brings hope to cancer patients who are traditionally considered "incurable."

If CAR-T cells no longer need to be “prepared and used immediately” and “customized”, the cost of treatment will be greatly reduced, which can further benefit more patients with malignant tumors.

Therefore, some scholars have begun to propose the use of "off-the-shelf" CAR-T cells for treatment. This therapy uses allogeneic sources, that is, CAR-T cells prepared from T cells from other people. Usually, T cells are collected from healthy donors or directly used from stem cells. After matching with the patient, the successfully designed CAR is "installed" on the surface of these T cells. The use of off-the-shelf CAR-T cell therapy can provide a simplified manufacturing solution and can even produce "off-the-shelf" products. In theory, they can be used at any time like other drugs without waiting.

Schematic diagram of T cells attacking tumor cells

Source: istockphoto.com

In addition to CAR-T therapy, other cell therapies are also moving towards the direction of achieving “spot availability”. I believe that in the future more patients with advanced cancer will have “access to drugs” and “can afford drugs”.

Source: Digital Beijing Science Center