Cell therapy’s next chapter: Industry embraces in-vivo innovation

The world of cancer treatment is entering a new chapter in 2025. For more than a decade, CAR-T therapy transformed life for those fighting blood cancers. However, traditional CAR-T (called ex vivo CAR-T) is expensive, complex and available in limited centers. Patients wait for weeks for their cells to be processed and returned. For fast moving cancers such delays can sometime be deadly.

A new approach to tackling these challenges is now rapidly emerging. With the introduction of in-vivo CAR T method, the engineering of T Cells happens inside the patient’s body, not in a laboratory. This could make the treatment faster, safer, and more widely accessible. Now this idea is no longer just talk. Multi-billion-dollar investments are being made for development and capacity building of this new method. Fast progress seen in 2025 is not just hype. Major deals and clinical programs show rising confidence.

• AbbVie acquires Capstan Therapeutics for $2.1 billion: AbbVie’s acquisition of Capstan signals intent to lead in mRNA-LNP technology, the same technique behind COVID-19 vaccines, now adapted for cancer.

• AstraZeneca buys EsoBiotec for $425 million: AstraZeneca expands its oncology pipeline and in vivo capabilities by acquiring a major player in non-viral gene delivery

• Kite Pharma (Gilead) acquires Interius BioTherapeutics for $350 million: Kite, a legacy ex vivo CAR-T leader, now positions itself toward vivo lentiviral vector platforms to stay competitive

What is CAR-T therapy?

Traditional CAR-T therapy uses a patient’s own immune cells. Doctors collect T-cells, take them to a lab, equip them with new “antennae” (chimeric antigen receptors, CARs) and infuse them back[nature]. These engineered CAR-T cells then find and destroy cancerous cells. While this strategy has saved lives, especially in leukemia and lymphoma, it comes with several serious challenges:

• Patients’ T-cells are extracted, shipped, modified, and returned; a process often takes weeks.

• It can cost hundreds of thousands of dollars per patient (not including hospital bills)

• Many eligible patients are never able to receive it due to limited facilities and logistical hurdles

In Vivo CAR-T: The new approach

In Vivo CAR-T therapy solves these problems by delivering genetic instructions into the body, turning ordinary T-cells into cancer fighters inside the patient. This can be done by injecting the necessary genes or mRNA, packaged in viral vectors (like lentivirus or adeno-associated virus) or non-viral systems (such as lipid nanoparticles). No apheresis, no complex manufacturing: just a simple injection or infusion.

The science behind in Vivo CAR-T

• Viral Vectors

Modified viruses (lentivirus, AAV) are used to deliver the CAR genes. These can provide stable, long-term CAR expression but raise safety questions due to potential gene integration risks.

• Non-Viral Systems

Lipid nanoparticles (LNPs) with mRNA, inspired by COVID-19 vaccines, can deliver transient CAR expression. This approach is scalable, may carry fewer long-term risks, and allows precise control over CAR presence, lowering the risk of side effects.

Key advantages over ex vivo therapy

• Manufacturing simplicity: Skipping lab manipulation means lower costs and fewer logistics failures. Instead of custom therapies for each person, off-the-shelf solutions become possible.

• Speed: Patients can be treated without long waits, crucial for aggressive cancer.

• Access: More hospitals will be able to administer treatment, even in low-resource settings.

• Potential for solid tumors: Re-engineering T-cells inside the patient—potentially many times—not only helps in blood cancers but might pierce the defenses of solid tumors, historically a challenge

• Wider applications: Expanding use into autoimmune and fibrotic diseases is already being explored in 2025 trials

Points of friction

In-Vivo CAR-T therapy holds considerable promise, but several challenges and limitations remain. One major concern is safety, particularly the need to ensure that genetic engineering tools precisely target T-cells without modifying other cell types, as off-target effects could lead to serious complications. The durability of response is another issue, since transient approaches such as mRNA-based delivery may require repeated administration, while viral vectors like AAV, although capable of longer persistence, carry risks of insertional mutagenesis and uncontrolled expression. Immune reactions also pose a barrier, as the patient’s immune system may recognize and neutralize viral vectors or even attack the engineered T-cells themselves, thereby diminishing therapeutic efficacy. Furthermore, solid tumors present unique hurdles, including dense stromal barriers, immunosuppressive signaling within the tumor microenvironment, and poor trafficking of engineered T-cells, all of which significantly hamper the effectiveness of CD19-like CAR-T strategies traditionally used in blood cancers.

Clinical trials and real-world momentum

Recent studies and trials in 2025 show that in-vivo CAR-T can deplete tumor cells or wipe out pathogenic B-cells in animal models and early human tests. For solid tumors, sequential and multi-antigen strategies enabled by mRNA show promise. Autoimmune “immune reset” therapies are being evaluated in monkeys and humanized mice. First-in-human trials for in vivo CAR-T are underway with patient enrollment documented across the US, Europe, and Asia-Pacific.

Industry impact and the future

Pharmaceutical leaders made multi-billion-dollar investments in in-vivo CAR-T platforms throughout 2025, driven by robust venture capital infusion and strategic partnerships between major corporations and innovative biotech startups. This surge in funding has accelerated clinical development and resulted in forecasts of over 100 publicly disclosed in vivo CAR-T assets by year-end. If current progress continues, these therapies could transform CAR-T into a truly “drug-like” modality—administered easily in standard hospital settings, bypassing the need for complex cell engineering labs.

Transformative potential

The advent of in-vivo CAR-T platforms could finally unlock the technology’s efficacy against solid tumors, a major challenge for traditional ex-vivo CAR-T approaches. Developers are also exploring CAR-T for autoimmune diseases, extending their reach far beyond oncology. As delivery techniques such as lipid nanoparticles or viral vectors become more refined, treatment costs are set to decline, making these advanced therapies affordable and accessible globally, not solely in wealthy regions.

Market and partnerships

With global investment exceeding $2 billion, pharma companies like AbbVie and Novartis, together with partners such as Capstan and Vyriad, are spearheading this next-generation therapeutics revolution. These partnerships reflect a dynamic pipeline, as well as a shift toward scalable, off-the-shelf treatments promising shorter timelines and more consistent patient access worldwide

The views and opinions are the author’s personal views