In previous installments, we’ve explored the fundamentals of CAR-T, the features of the in vivo model, gene delivery strategies, target antigens, and intracellular signaling.
In previous installments, we’ve explored the fundamentals of CAR-T, the features of the in vivo model, gene delivery strategies, target antigens, and intracellular signaling. In this fifth edition, we shift our focus to clinical applications. What clinical trials are currently underway? Which companies are leading the charge to bring in vivo CAR-T to patients? In this article, we present the current landscape in a clear and accessible format.
Table of Contents
- 1. In Vivo CAR-T Clinical Trials Have Begun
- 2. Key Developers: Capstan, Intellia, Umoja and More
- 3. Technology Approaches and Target Indications
- 4. Challenges and Forecasts
- 5. Summary and Next Preview
1. In Vivo CAR-T Clinical Trials Have Begun
CAR-T therapy, once considered a futuristic dream, has already produced multiple FDA-approved ex vivo therapies for hematological malignancies. Yet, these traditional therapies are costly, time-intensive, and infrastructure-dependent. The promise of in vivo CAR-T—generating CAR-T cells directly inside the patient’s body—has drawn growing attention.
From 2023 to 2024, multiple in vivo CAR-T human clinical trials were launched, particularly in the U.S. These trials represent a shift from proof-of-concept to practical validation of safety and efficacy.
2. Key Developers: Capstan, Intellia, Umoja and More
Let’s introduce the key players pioneering in vivo CAR-T development.
● Capstan Therapeutics
Capstan utilizes lipid nanoparticles (LNPs) to deliver mRNA directly into T cells in vivo. The company received FDA IND approval in 2023 and launched the world’s first human trial targeting CD19+ B-cell leukemia and lymphoma.
Update (May 2026): AbbVie completed its acquisition of Capstan Therapeutics on August 19, 2025 (up to $2.1B). Capstan now operates as an AbbVie subsidiary, with its lead asset CPTX2309 (CD19 in vivo CAR-T for autoimmune diseases) advancing in AbbVie’s immunology pipeline. Together with Eli Lilly’s acquisitions of Orna (Feb 2026) and Kelonia (Apr 2026), Kite/Gilead’s acquisition of Interius (Aug 2025), and AstraZeneca’s acquisition of EsoBiotec (May 2025), the in vivo CAR-T field has shifted from independent startups to large-pharma platforms.
● Intellia Therapeutics
Famous for its CRISPR gene editing, Intellia is developing in vivo gene-edited CAR-T using LNPs. Their long-term vision includes not only oncology but also autoimmune disease applications.
● Umoja Biopharma
Umoja leverages a viral vector technology called VivoVec™ for in vivo CAR integration. The company also focuses on tunable co-stimulatory signaling for enhanced CAR-T durability and safety.
● Other Notables
- Vector BioPharma: Organ-specific promoters for targeted in vivo CAR delivery
- Sana Biotechnology: In vivo T-cell programming technologies
- Verve Therapeutics: Early-stage work in epigenetic control for CAR expression
3. Technology Approaches and Target Indications
The leading approaches can be divided into two broad categories:
- 1. LNP-based mRNA delivery: Non-viral, lower immunogenicity, easier to manufacture. Used by Capstan and Intellia.
- 2. Viral vector delivery: High efficiency and tissue specificity but with concerns about immunogenicity and insertion risks. Used by Umoja and Vector.
While B-cell malignancies (e.g., leukemia, lymphoma) remain the initial focus, expansion into multiple myeloma, AML, and even solid tumors is actively underway.
4. Challenges and Forecasts
Despite recent momentum, several key challenges remain:
- Target selectivity: Ensuring CAR genes are delivered only to T cells
- Long-term safety: Avoiding off-target toxicity or excessive immune activation
- Limited clinical data: Most trials are in early Phase 1
Nevertheless, these are no longer hypothetical issues. As Phase 1/2 trials progress, we expect interim results by 2025, potentially paving the way for accelerated development in the next 2-3 years.
5. Summary and Next Preview
In vivo CAR-T has advanced from concept to clinic. Capstan, Intellia, Umoja, and other leaders are rewriting what’s possible in cellular immunotherapy. These companies aren’t just aiming to improve CAR-T—they’re aiming to make it accessible, scalable, and safer.
In our next edition (#6), we will dive into solutions to remaining challenges: how researchers are improving targeting precision, minimizing side effects, and engineering smart control systems into in vivo CAR-Ts.
🔗 Related Articles / Series Links
- Therapeutic Trends 2025: What to Watch
- Introductory Series Index
- #1: What Is CAR-T? The Story of Emily Whitehead
- #2: The Technologies Behind In Vivo CAR-T
- #3: Key to Precision and Safety: Designing Smart CAR Expression
- #4: Deep Dive into CAR Structure: The Latest in Co-stimulation and Signal Engineering
This article was produced by the Morningglorysciences editorial team.
Editor’s Note (May 2026 Update): The Industrial Reordering of In Vivo CAR-T
This article was originally written in July 2025, when many of the in vivo CAR-T players profiled above were still independent biotechs. Since then, the field has consolidated rapidly through Big Pharma M&A, and the "startup landscape" we described has effectively become a "four-platform landscape" built around large pharmaceutical owners.
Key transactions readers should be aware of when revisiting the players in this article:
- Capstan Therapeutics → AbbVie (acquisition completed August 19, 2025; deal value up to ~$2.1 billion). CPTX2309, the LNP-mRNA CD19 in vivo CAR-T for autoimmune indications, is now advancing inside AbbVie’s immunology pipeline.
- EsoBiotec → AstraZeneca (acquisition completed May 2025). EsoBiotec’s engineered lentiviral vector platform brings AstraZeneca a clinical-stage in vivo CAR delivery technology.
- Interius BioTherapeutics → Kite Pharma (Gilead) (acquisition announced August 21, 2025). Interius’s targeted lentivirus platform expands Kite’s presence beyond its established ex vivo CAR-T franchise.
- Kelonia Therapeutics → Eli Lilly (acquisition announced April 20, 2026; deal value up to ~$7 billion). Kelonia’s in vivo Genetic Medicine Platform (iGMP) gives Lilly a flagship in vivo CAR-T capability.
- Orna Therapeutics → Eli Lilly (acquisition announced February 9, 2026; deal value up to ~$2.4 billion). Orna’s circular RNA / LNP technology adds another delivery modality to Lilly’s portfolio.
- Umoja Biopharma remains independent as of this writing and continues to develop its VivoVec lentiviral platform.
The structural takeaway: AbbVie, Eli Lilly, Gilead/Kite, and AstraZeneca are emerging as the four platform-owning incumbents of in vivo CAR-T, while Novartis and BMS continue to anchor the ex vivo CAR-T franchise (Kymriah, Breyanzi, Abecma). The clinical-trial frontiers described in this article still read accurately at the science level, but the corporate ownership of those frontiers has shifted decisively from independent biotechs toward Big Pharma platforms during late 2025 through early 2026.
Companion deep-dive: In vivo CAR-T – Convergence of Platforms (Series Summary).
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