Research results have emerged showing that treatment genes can be delivered into the body like a coronavirus vaccine, enabling patients to create their own living anti-cancer agents and destroy cancer cells. It involves generating CAR-T cells, often referred to as "living drugs" or "serial killers" of cancer cells, which proliferate and continue to kill cancer cells once they are introduced into the body.
Until now, CAR-T, developed as a treatment for blood cancer, involved extracting patient cells, creating them outside the body, and then reinjecting them, which was costly and time-consuming. If this can be generated directly in the patient's body, it is expected that anyone can easily receive treatment.
◇Animal experiments prove effectiveness in eliminating blood cancer cells
A research team led by Professor Carl June at the University of Pennsylvania School of Medicine noted on the 20th in the international journal "Science" that they proposed a new method for producing CAR-T cells in the body by directly delivering messenger ribonucleic acid (mRNA), which creates proteins that bind to cancer cells, into the T cells.
CAR-T cells refer to T cells that have "Chimeric Antigen Receptors (CAR)." Like the chimera of Greek mythology, which has the forms of various animals, this means that a protein binding to the antigens present only in cancer cells has been combined with T cells, the immune cells.
CAR-T can only bind to cancer cells, so it does not accidentally attack normal cells like other anti-cancer drugs. This contributes to its effectiveness and minimizes side effects, making it akin to soldiers that have intelligence to locate the enemy. CAR-T cell therapies have shown groundbreaking therapeutic effects in blood cancers where there were no previous drugs. Since 2017, seven types of therapies, after Novartis's Kymriah and last year's Aucatzyl from U.K.'s Autolus Therapeutics, have received approval from the U.S. Food and Drug Administration (FDA) for blood cancer treatments.
The issue is the expense. Because patient T cells are extracted and genes to create the protein for cancer cell detection are added, significant time is required in dedicated facilities, and thus treatment costs have increased. Treatment can cost up to $500,000 (680 million won) per session.
Professor June demonstrated that the CAR-T production process could be resolved inside the body, dramatically reducing the development time and expense of therapies. mRNA copies some of the genetic information from DNA to synthesize proteins within cells. The research team wrapped the mRNA for creating the CAR protein that sticks to cancer cells in lipid nanoparticles, similar to a coronavirus vaccine. Proteins that bind to T cells were attached to the surfaces of the lipid nanoparticles. When the lipid nanoparticles bind, the mRNA enters the T cells, and the CAR protein that sticks to cancer cells is produced on the surface.
CAR-T therapies are used to treat B-cell lymphoma among blood cancers. B-cell lymphoma is cancer that develops from B cells, a type of white blood cell. B cells create antibodies to fight external invaders, but when they proliferate abnormally or transform, lymphoma occurs.
The research team induced human B-cell lymphoma in mice and then injected lipid nanoparticles wrapped with mRNA. Within days, they completely eliminated the cancerous B cells. The same effect was observed in monkeys, which are primates like humans, increasing the possibility of commercialization.
◇One-time CAR-T treatment without changing genes
Several companies are already testing methods to generate CAR-T cells from patients' bodies. They have used harmless viruses as vectors to deliver CAR genes into T cells. Interius BioTherapeutics in the U.S. has been conducting clinical trials on CAR-T cells created via a viral vector method since October last year. They presented initial results of clinical trials targeting patients with non-Hodgkin lymphoma at an international conference in February. According to the company, two patients who received low doses showed no effects, but one patient who received a high dose had all cancerous cells disappear after six days.
Umoja Biopharma in the U.S. is also conducting clinical trials on blood cancer patients in both the U.S. and China. They expect results by the end of this year. Belgium's EsoBiotec has also been conducting clinical trials for CAR-T in patients with multiple myeloma in China since January, using a viral vector method. The company reported that the first patient had no detectable cancer cells one month post-treatment. In March, U.K. pharmaceutical company AstraZeneca signed an agreement to acquire EsoBiotec for up to $1 billion (1.36 trillion won).
Professor June's method of in-body CAR-T is distinct in that it is a one-time treatment that does not alter the genes of T cells. Whether using an in-body or ex-body viral vector to deliver genes, the genes of T cells can be permanently altered. Should mutations occur, it could lead to issues where it targets incorrect cells instead of cancer cells. Professor June's team allowed mRNA to create CAR proteins outside the cell nucleus with the gene, instead of inserting the CAR gene into the T cell DNA. The mRNA naturally degrades over time.
Professor June has developed the in-body CAR-T technology using the mRNA method with Capstan Therapeutics in the U.S. They plan to enter clinical trials involving humans either this year or next. Capstan was founded by Professor Carl June, a pioneer of CAR-T technology, and Professor Drew Weissman, who developed mRNA vaccine technology at the same university and received the Nobel Prize in Medicine in 2023.
Dr. Stephen Gottschalk at St. Jude Children's Research Hospital in the U.S. commented in a paper published in Science on the same day, saying, "The in-body CAR-T method using lipid nanoparticles to deliver mRNA is ideal for cancer treatment where genetically modified CAR-T cells do not need to remain in the human body for long." This is because even if all cancer cells are eradicated, having CAR-T cells remain in the human body could potentially trigger mutations that lead to another disease.
Conversely, Professor Karin Straathof of University College London (UCL) pointed out the limitations of one-time CAR-T treatments. He noted that "this method is a much simpler way to manufacture CAR-T cell therapies, thus reducing expenses," but added, "the traditional CAR-T cells have the advantage of providing long-term protection to the human body; however, this approach only temporarily generates these cells, so additional injections will be necessary if cancer recurs." He also stated that since clinical trials have not yet been conducted, it is impossible to ensure effectiveness or safety.
References
Science (2025), DOI: https://doi.org/10.1126/science.ads8473
Science (2025), DOI: https://doi.org/10.1126/science.ady7928