There is a cell therapy that is referred to as ‘living medicine’ and ‘a chain killer of cancer cells’ because it continues to kill cancer cells while proliferating once introduced into the body. It is CAR-T cells. CAR stands for chimeric antigen receptor. Like the chimera in Greek mythology, which has features of various animals, it means that a gene that detects antigen proteins on the surface of cancer cells has been combined with the immune T cells. Unlike other anticancer drugs, it leaves normal tissues unharmed and only attacks cancer cells, resulting in excellent therapeutic effects.
In particular, CAR-T cell therapy has shown groundbreaking therapeutic effects for blood cancer, where there were previously no effective medications. Following Kymriah from Novartis in Switzerland in 2017, seven types of blood cancer therapies have received approval from the U.S. Food and Drug Administration (FDA), including Aucatzyl from Autolus Therapeutics in the UK last year. According to Polaris Market Research & Consulting, the CAR-T therapy market was about 10 trillion won last year and is projected to grow to over 15 trillion won this year, exceeding 256 trillion won by 2034.
The issue is the expense. Extracting the patient’s T cells and adding genes requires a considerable amount of time in specialized facilities. Consequently, treatment costs have also increased. One treatment can cost around $500,000 (680 million won). The international journal Nature reported on the 27th of last month that scientists are developing ways to drastically reduce the cost of therapies. The method involves easily transforming T cells into the most suitable form for cancer treatment within the body. If commercialized, it could allow for easier administration by patients, thereby expanding the market. A new era of living anticancer drugs is emerging.
◇Detection capability of cancer cells granted inside the human body
The existing ex vivo method for producing CAR-T cells takes weeks. First, T cells are extracted from the patient’s body, and genes that target cancer cells are delivered. At this point, a gene for CAR proteins that bind to cancer cells is inserted into a virus that has been modified to remove its toxicity, and the T cells are infected. This causes the CAR gene to insert itself into the T cell’s genome, creating receptors on the surface that bind to cancer cells. Finally, the genetically modified T cells are proliferated and reinfused into the body. The T cells then automatically locate and attack cancer cells, with their detection capability ingrained in their genes for generations.
Recently, scientists have been implementing this entire process within the human body. The principle is similar to the ex vivo method. The key to developing in vivo CAR-T cells is accurately delivering the genes specifically to the T cells. The ex vivo method avoids affecting other cells by extracting and adding genes only to T cells, but when done inside the body, the gene that locates cancer cells could mistakenly go to incorrect cells. Companies have developed various methods to resolve this issue.
Interius BioTherapeutics in Philadelphia, Pennsylvania, is testing viral vectors that uniquely bind to proteins on the surface of immune T cells and natural killer (NK) cells. Umoja Biopharma in Washington has developed a viral vector that simultaneously binds to three proteins on the T cell surface. The company has reported that in animal tests, its method was more effective at locating T cells than a viral vector that binds to only one protein.
The existing ex vivo method for CAR-T cell production cannot be performed at just any hospital. Patients must go to specialized facilities operated by the companies and stay there for weeks. If CAR-T cells are produced inside the body, there is no need for separate genetic modification or cell culture facilities, reducing the expense to one-tenth. Time is also significantly shortened, and the burden on the human body is less.
In the existing ex vivo method, all T cells in the body are eliminated before reinfusing the genetically modified CAR-T cells. This creates space for the later growth of the genetically modified T cells. However, when producing CAR-T cells inside the body, this step is unnecessary.
◇mRNA vaccine method also utilized
Interius has been conducting clinical trials of in vivo CAR-T cells produced with the viral vector since October of last year. In February, it announced early clinical trial results for patients with non-Hodgkin lymphoma at an international conference. According to the company, two patients who received a small dose showed no effect, but a patient who received a larger dose had all cancerous cells disappear within six days.
Umoja Therapeutics is conducting clinical trials on blood cancer patients in the U.S. and China, with results expected by the end of this year. EsoBiotec in Belgium has also produced CAR-T cells inside the body using viral vectors. The company has been conducting clinical trials on patients with multiple myeloma in China since January. The company stated that cancer cells were undetectable in the first patient one month after treatment. In March, UK pharmaceutical company AstraZeneca announced it had reached an agreement to acquire EsoBiotec for up to $1 billion (1.36 trillion won).
Regardless of whether it is in vivo or ex vivo, CAR-T cells that deliver genes via viral vectors modify the genes themselves. If mutations occur, they might not target cancer cells but could attack inappropriate cells instead. To address this, a method has been developed that produces proteins that bind to cancer cells only when treating T cells.
mRNA COVID vaccines contain information for producing the spike protein of the coronavirus in the form of mRNA. Once inside the body, it induces an immune response by creating the virus’s spikes and prompting antibody production. Similarly, mRNA that synthesizes proteins binding to cancer cells is delivered to T cells. The mRNA only produces the corresponding protein once and then degrades. It is essentially a one-time use method for producing CAR-T cells.
Capstan Therapeutics in California and Orna Therapeutics in Massachusetts have developed technology to attach mRNA to nanoparticles to deliver it to T cells. The two companies plan to enter clinical trials this year or next.
◇Stars of the bio academia all gather
T cells have been developed as therapies since the 1980s. Initially, the methods involved simply increasing the number of T cells outside the body and then reinfusing them into patients. However, the effect did not last long. T cells must receive signals from dendritic cells, which have a branched shape, to detect cancer cells. Even if the number of T cells increased, they were ineffective without the signal from the scouts.
In the 1990s, researchers at the University of Pennsylvania attempted to treat AIDS by exposing T cells extracted from the body to dendritic cells. However, due to the individual variability of dendritic cells, it was not very effective. As an alternative, they also used protein particles designed to mimic dendritic cells to stimulate T cells. While there was a significant proliferation effect of T cells, their ability to locate cells that cause diseases was weak.
Cancer cells are adept at evading attacks from immune cells. Starting from healthy cells, even a slight alteration in their shape can lead immune cells to misidentify them as normal cells and avoid attacking them. Researchers at the University of Pennsylvania developed a method in the 2010s to alter T cells' genes so they could bind specifically to antigen proteins found solely on cancer cells. This method is what we now know as CAR-T cells. The journal Science selected CAR-T as the ‘Breakthrough of the Year’ in 2013.
Now, more than a decade later, the CAR-T cells have evolved to the point where they can also be produced inside the body. Once commercialized, the market could expand even further. This is why global scientists are converging on developing in vivo CAR-T.
Capstan Therapeutics was founded by Carl June, a pioneering figure in CAR-T technology at the University of Pennsylvania, along with Drew Weissman, who developed mRNA vaccine technology and won the 2023 Nobel Prize in Medicine.
Azalea Therapeutics in California was founded by Professor Jennifer Doudna from the University of California, Berkeley. Professor Doudna received the 2020 Nobel Prize in Chemistry for developing the CRISPR gene-editing tool. Azalea is developing technology to deliver cancer cell detection genes to T cells inside the body using nanoparticles and viral vectors.
References
Nature(2025), DOI: https://doi.org/10.1038/d41586-025-01570-6
Science(2022), DOI: https://doi.org/10.1126/science.abm0594
Science(2018), DOI: https://doi.org/10.1126/science.aar6711
The New England Journal of Medicine(2013), DOI: https://doi.org/10.1056/NEJMoa1302369
Science(2013), DOI: https://doi.org/10.1126/science.342.6165.1432