In Vivo CAR-T: A New Chapter in Cell Therapy Delivery

CAR-T cell therapy has reshaped the treatment of B-cell malignancies over the past decade. However, the conventional ex vivo CAR-T model—which requires cell collection, genetic modification, and reinfusion—remains complex, costly, and difficult to scale.

In recent years, in vivo CAR-T has emerged as a promising alternative, aiming to engineer T cells directly inside the patient’s body. This approach could significantly simplify manufacturing while expanding access to CAR-T therapies beyond specialized centers.

Early Clinical Momentum Before Academic Breakthrough

Notably, clinical development in this field began moving forward even before large-scale academic validation was published.

In June 2025, Capstan Therapeutics announced the initiation of a Phase I clinical trial for CPTX2309, an in vivo CAR-T candidate targeting B-cell–mediated autoimmune diseases. The program uses targeted lipid nanoparticles (tLNPs) to deliver mRNA encoding CAR constructs directly to immune cells.

This marked one of the earliest clinical validations of the in vivo CAR-T concept.

Science Confirms the Concept

Later in June 2025, Science published a landmark study demonstrating in vivo CAR-T cell generation using targeted lipid nanoparticles. The study showed:

• Efficient and selective CAR expression in T cells

• Effective B-cell depletion

• Good tolerability in both murine and non-human primate models

• Immune effects consistent with a functional “immune reset”

Together, these results provided strong mechanistic support for the clinical direction already underway.

Industry Validation at Scale

The strategic importance of in vivo CAR-T became even clearer when AbbVie acquired Capstan Therapeutics in an all-cash deal valued at $2.1 billion.

The acquisition highlighted growing industry confidence in:

• In vivo genetic engineering approaches

• mRNA-based immune cell reprogramming

• Lipid nanoparticle delivery platforms beyond vaccines

Why Lipid Nanoparticles Matter

At the center of in vivo CAR-T development is lipid nanoparticle (LNP) design.

Targeted LNPs must balance:

• Circulation stability

• Controlled biodistribution

• Cell-specific uptake

• Efficient intracellular delivery

To achieve this, functional PEG-lipids play a critical role.

The Role of Functional PEG-Lipids

Phospholipid–PEG conjugates are widely used in LNP formulations to improve stability and enable site-specific ligand attachment.

Among them, DSPE-PEG-Maleimide is commonly used as a controllable interface for conjugating thiol-modified antibodies, peptides, or targeting ligands—an essential feature for cell-specific delivery in in vivo CAR-T systems.

Supporting Advanced mRNA and In Vivo CAR-T Research

To support advanced mRNA and in vivo CAR-T delivery research, Biopharma PEG offers a broad portfolio of functional PEG-lipids, including:

• mPEG-DSPE (MW 1K–20K)

• DSPE-PEG-NH₂ (MW 1K–20K)

• DSPE-PEG-MAL (MW 1K–20K)

• DSPE-PEG-Mannose (MW 1K–20K)

• DSPE-PEG-SC (MW 1K–20K)

• DSPE-PEG-c(RGDyK) (MW 2K, 3.4K, 5K, 10K, 20K)

These materials are designed to support early research, formulation optimization, and scale-up needs in next-generation mRNA and cell therapy platforms.

Looking Ahead

In vivo CAR-T is still at an early stage, but momentum is building rapidly. With clinical trials underway, strong academic validation, and major industry investment, the field is moving toward a future where CAR-T therapies may become:

• Faster to produce

• Easier to scale

• More accessible to patients worldwide

As delivery technologies mature, the combination of mRNA engineering, targeted lipid nanoparticles, and functional PEG-lipids is likely to define the next wave of cell therapy innovation.