When Bruce Levine and colleagues began developing engineered immune cells to fight cancer in the 1990s, their work was largely dismissed. “The wider community was very sceptical,” Levine, an immunologist at the University of Pennsylvania, told Nature. Often relegated to the final presentation slot at scientific meetings, their work on what would become CAR T cell therapy attracted little early attention.
Three decades later, that skepticism has given way to admiration. CAR T cells—engineered immune cells capable of targeting and destroying cancer cells—are now considered one of the most powerful tools available to treat blood cancers, and new research suggests they may be effective against solid tumors and autoimmune diseases. The global CAR-T therapy market is projected to balloon from $11 billion in 2024 to nearly $190 billion by 2034, according to one research firm.
Yet this powerful therapy comes with significant barriers. Traditional CAR-T therapy requires a complex, time-consuming ex vivo process in which T cells are extracted from a patient, genetically modified in a lab, and reinfused after amplification. The process can take weeks and costs around $500,000 per treatment, limiting its accessibility—only about 200 centers in the U.S. currently offer it.
Dr. Saar Gill, another CAR-T expert from the University of Pennsylvania, noted to Nature that this delay means many patients never receive the potentially life-saving treatment. “We all want to get to a situation where CAR T cells are more like a drug,” he said.
In Vivo Therapies: A New Era in Cancer Treatment
A new generation of biotech companies is now working to revolutionize CAR-T therapy by engineering T cells directly inside the body, an approach known as in vivo CAR-T. Instead of extracting and modifying T cells externally, this technique uses viral vectors or nanoparticles to deliver genetic material into immune cells while they’re still inside the patient.
Notably, this approach has attracted some of the biggest names in science. The founders of Capstan Therapeutics include Levine himself, along with Nobel laureates Carl June and Drew Weissman. Another company, Azalea Therapeutics, co-founded by CRISPR pioneer Jennifer Doudna, is also focusing on in vivo strategies. In a major sign of growing interest, AstraZeneca recently agreed to pay up to $1 billion for EsoBiotec, a Belgium-based firm developing in vivo CAR-T therapies.
Early clinical trials have begun. For example, Interius BioTherapeutics, co-founded by Gill, launched its first trial in October for patients with non-Hodgkin’s lymphoma. Though the first two patients didn’t respond to a low dose, a third patient who received a higher dose showed promising results, with B cells nearly eliminated for three months.
Meanwhile, Umoja Biopharma is running trials in both the U.S. and China, and EsoBiotec reported that its first patient had no detectable cancer cells just a month after treatment. Both Capstan and Orna Therapeutics are preparing to launch their own human trials using RNA-based delivery systems instead of viral vectors.
Speed, Cost, and Safety
The benefits of in vivo therapies are numerous. They could drastically cut treatment costs, allow for on-demand availability, and potentially bypass the need for chemotherapy, which is currently required to “clear space” for the engineered cells in traditional CAR-T therapy. Avoiding this step could make the therapy accessible to patients too ill to undergo chemotherapy.
Importantly, RNA-based approaches—like those being developed by Orna—may also improve safety. By delivering temporary genetic instructions, these therapies can be discontinued at the first sign of trouble, unlike viral methods that permanently alter the genome and may carry a small but real risk of secondary cancers.
Still, not all questions have been answered. As Nature notes, researchers remain cautious about whether in vivo methods can match the long-term efficacy of ex vivo approaches. “Will you ever cure cancer without having permanently modified T cells?” asked Christian Buchholz of Germany’s Paul Ehrlich Institute.
A Rapidly Evolving Field
Despite the open questions, momentum is building. Nature reports that “everyone and their brother wants to get in the field,” quoting Levine. Companies are not only racing to develop in vivo methods but also improving the ex vivo model, such as AstraZeneca’s acquisition of a firm capable of producing CAR T cells in just 22 hours.
As clinical trials expand and early data rolls in, 2025 and 2026 are poised to be transformative years for CAR-T innovation. Whether through in vivo delivery, RNA platforms, or ultra-fast manufacturing, the goal is the same: make this life-saving therapy simpler, cheaper, and available to all who need it.
