--- title: "The innovators working to make in vivo cell therapy a reality" type: "News" locale: "en" url: "https://longbridge.com/en/news/283126417.md" description: "As in vivo cell therapies enter clinical trials, suppliers are addressing technical and logistical challenges to ensure commercial viability. Recent acquisitions by major pharmaceutical companies, such as AstraZeneca's $1bn purchase of EsoBiotec, highlight growing interest in this field. In vivo therapies, which deliver genes directly to patients, are still in early development stages, with most players in preclinical or Phase I trials. The next year is crucial for gathering more data on these therapies, which are often misclassified as traditional cell therapies but are more akin to gene therapies." datetime: "2026-04-17T09:44:22.000Z" locales: - [zh-CN](https://longbridge.com/zh-CN/news/283126417.md) - [en](https://longbridge.com/en/news/283126417.md) - [zh-HK](https://longbridge.com/zh-HK/news/283126417.md) --- # The innovators working to make in vivo cell therapy a reality First-in-human studies are now trialing in vivo CAR-T therapies, manufacturing therapeutic cells within the patient. Photo by Design Cells/iStock via Getty Images. As investors signal early interest in _in vivo_ cell therapies and raise the modality’s potential for commercial success, a growing industry of suppliers is innovating to safeguard their viability. Cell therapy involves transfecting live cells to express a gene of interest, thereby altering the cells’ function. Unlike existing _ex vivo_ treatments that engineer patient cells before injecting them, investigational _in vivo_ cell therapies deliver the gene to patients directly through a vector such as a modified virus or a lipid nanoparticle (LNP). ### Go deeper with GlobalData - ![ReportsLogo](/wp-content/themes/goodlife-wp-B2B/assets/img/report.png) Reports #### NPVM: Alaunos Therapeutics Inc's Gene-Modified Cell Therapy to Targ... - ![ReportsLogo](/wp-content/themes/goodlife-wp-B2B/assets/img/report.png) Reports #### Immuno-oncology in Pharmaceuticals: Cancer chimeric antigen recepto... ##### Go deeper with GlobalData The gold standard of business intelligence. Find out more #### Discover B2B Marketing That Performs Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms. Find out more The rapid pace of development in this space is evident in a series of recent high-profile acquisitions. In March 2025, AstraZeneca’s landmark $1bn acquisition of in vivo developer EsoBiotec stood out at the cell and gene therapy (CGT)-focused Advanced Therapies conference held in London.   The 2026 edition of the same event was set against the backdrop of several more deals; Eli Lilly acquired Orna Therapeutics in February 2026 for $2.4bn, after AbbVie and Bristol Myers Squibb announced billion dollar acquisitions in H2 2025. A sizeable uptick in dedicated sessions at the 2026 conference was reflective of the field’s increasing maturity, accruing big pharma interest and a growing industry of suppliers innovating to solve the technical and logistical challenges faced by this new class of therapies. ## In vivo has gone clinical As one of the latest innovations in the cell therapy space, _in vivo_ therapies are still in early development. “Most of the players in the field are \[in\] either preclinical stage or Phase I,” explains Davide Zocco, head of commercial development for exosomes and mRNA-LNPs for the Swiss CDMO Lonza. Nonetheless, Zocco notes the high-value deals by big pharma with _in vivo_ biotechs, a signal of the modality’s potential. These big pharma-biotech acquisitions were made with very little clinical data, notes Devid Peritt, founder and CSO of Texas-based Lupagen, which develops bedside cell therapy delivery systems. AstraZeneca’s acquired _in vivo_ CAR-T is being studied in a Phase I trial (NCT06791681) that recently had an interim readout. A 2026 Nature paper reported that in five multiple myeloma patients, four had an objective response and three had complete remission. Before this, Massachusetts-based biotechs Create Medicines, which is developing _in vivo_ CAR-myeloid (CAR-M) treatments, and Kelonia Therapeutics, which is testing its _in vivo_ CAR-T therapy KLN-1010, both released early data in late 2025, as per company press releases. The next 12 months will be pivotal as more comprehensive data for _in vivo_ cell therapies emerges, according to Adam Inche, CEO and founder of the Scottish company Lentitek, an innovator of viral vectors. He says investors are eager, but the technology’s risks remain to be fully understood. ## Positioning in vivo cell therapies in the CGT space Despite its widespread use, the term ‘_in vivo_ cell therapy’ is a misnomer, according to Inche. He says they are more like gene therapies, with the key difference being that a gene therapy typically corrects faulty functions in a cell, while _in vivo_ cell therapies seek to introduce an entirely new function to a cell so that it itself acts therapeutically. This is reflected in FDA guidance for gene therapy products, which does not clearly distinguish _in vivo_ therapy, or indeed separate cell and gene therapies, grouping all as ‘gene therapy’ or ‘genomic modification’. Use of the term ‘_in vivo_’ is largely tied to perception and marketing, in Inche’s view, an attempt to build on the success of _ex vivo_ cell therapies like chimeric antigen receptor therapies (CAR-Ts). Kella Kapnisi, head of cell and gene therapy at Cambridge, UK-based medical device consultancy Team Consulting, agrees these treatments could be classified as gene therapy. A cornerstone of the appeal for _in vivo_ therapies is the promise of having the capability of off-the-shelf allogeneic cell therapies, but free from the requirements for complex processing, transport, and storage of live cells. _In vivo_ therapies shed many technical challenges that plague _ex vivo_ therapies, says Peritt, but in doing so have inherited the limitations of gene therapies. * * * _**Lentitek: Solving for splicing**_ _In the case of lentiviral in vivo therapies, a lentiviral vector transfects one host cell type with a genetic payload that causes it to target a second host cell type. As lentiviruses are replicated in manufacturing, the genetic payload can sometimes be cut—or spliced—producing an incomplete genetic payload._ _Due to this, the vector may express the gene and transfect the wrong cell. Lentitek has developed a genetic element that prevents splicing during lentiviral vector production to address this issue._ * * * ## Technical hurdles spur supplier-side innovation According to Peritt, there are three main technical problems for _in vivo_ therapies: dosing accuracy, as the number of circulating altered cells cannot be directly controlled; off-target effects, as the vectors may target non-target cells; and immunogenicity, as the host immune system attacks the vectors. Different vectors offer varying solutions, according to Zocco. Viral vectors offer durable integration of genes into host cells, but risk producing pro-cancer genetic changes. They are also prone to causing an immune response. Zocco notes that LNPs can instead transiently express an mRNA payload. While less durable compared to lentiviral vectors, LNPs are more controllable and easier to manufacture. But they too can elicit an immune response and are known to preferentially target liver cells. * * * _**Lupagen: Taking in vivo ex vivo**_ _Lupagen’s Xynvivo system changes the way an in vivo cell therapy is administered. Peritt compares it to a dialysis machine; a patient’s blood cells are extracted, transfected, filtered, and returned to them, all at the bedside in a continuous loop._ _Unbound vectors are filtered out before cells reenter the patient, preventing an immune reaction triggered in response to them. Transfecting cells outside the patient allows for precise cell type targeting and control over dosing. Xynvivo blurs the line between in vivo and ex vivo, as per Peritt._ * * * ## A unique logistical landscape Experts hope that _in vivo_ therapies can tackle crucial logistical challenges that have stifled commercial success for many cell therapies, particularly autologous ones. Off-the-shelf _in vivo_ treatments that use the patient as a ’manufacturer’ would ease the complexity and cost of delivering a therapy. But they recognise that scalability remains a limiting factor. Complex genetic editing is out of scope for current _in vivo_ technologies. For now, experts say these factors leave an enduring space for _ex vivo_ treatments and would likely mean both modalities coexist rather than one replacing the other. * * * _**Lonza: Consolidating supply**_ _The material supply network for in vivo therapies is still nascent, says Zocco. For example, there are only two or three suppliers for ionisable lipids used to create LNP vectors with lower toxicity, he says. Many cutting-edge materials and technologies also require expensive licensing fees._ _As a CDMO, Zocco describes Lonza’s role as, “to de-risk the technical path for commercialisation.” The CDMO provides an established manufacturing platform and covers licensing fees to offer developers “freedom to operate,” according to Zocco._ * * * **_Team Consulting: Scaling out vs scaling up_** _Not only do different therapies often require varying manufacturing processes, but several personalised therapies need to be tailor-made for each patient. Hence, a unified, standardised global supply chain system may not work for in vivo therapies._ _Team Consulting has sought ways to ‘scale-out’ personalised therapy production rather than ‘scale-up’. For example, Kapnisi says the company supported the design of the NANOme device for the German pharmaceutical equipment supplier LEON. This device encapsulates genetic payloads in LNPs for single-patient batches, offering cost-effective small-scale production better suited to personalised in vivo._ * * * Despite these challenges, Peritt says _in vivo_ therapies benefit from a foundation laid by earlier generations of cell therapies and afford simpler manufacturing compared to _ex vivo_ cell therapies. No costly, sensitive cell handling is required, only vector manufacture, a process already well-established for _ex vivo_ cell therapy supply. Expanding production to meet commercial needs is feasible, according to Kapnisi. _In vivo_ developers must learn from prior cell therapies and scale production early in the clinical phase. She says this can be done, but investors need to back these efforts with cash, against their instincts to hold back capital until late-phase readouts. _Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva_. _Editorial content is independently produced and follows the_ highest standards _of journalistic integrity. Topic sponsors are not involved in the creation of editorial content._ #### Free eBook ### Navigating cell therapy process development The cell therapy manufacturing sector is rapidly evolving, driven by the need to balance innovative process development with rigorous GMP standards. This eBook, brought to you by industry leaders Cytiva, explores how biotech firms can address common challenges — including minimizing contamination risks from manual processes, overcoming resource limitations, and creating scalable, robust designs. Industry experts discuss strategies including automation, strategic outsourcing, and flexible equipment selection to streamline processes and reduce regulatory risks. To unlock expert insights on optimizing your cell therapy pathway from clinical development to commercialization, fill in your details now. **Thank you.** You will receive an email shortly. Please check your inbox to download the eBook. By Cytiva Thematic You have a right to withdraw your consent at any time, by clicking here. We may still continue to send you service-related and other non-promotional communications. 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