In Vivo CAR-T Therapy in 2026: Are We About to Change How Cell Therapy Is Made?

What if CAR-T therapy no longer required collecting a patient’s immune cells, sending them to a specialized manufacturing facility, genetically engineering them, expanding them, testing them, and returning them weeks later?

What if the patient’s own body could be used to generate CAR-T cells directly inside the patient?

That is the central promise of in vivo CAR-T therapy.

Instead of manufacturing a personalized cellular product outside the body, in vivo CAR-T approaches aim to deliver genetic instructions directly to immune cells inside the patient. The goal is to transform those cells into therapeutic CAR-T cells without the traditional ex vivo manufacturing workflow.

In 2026, this concept is moving beyond early laboratory research. Multiple companies have entered clinical development, while major pharmaceutical companies have committed billions of dollars to platforms using lipid nanoparticles, lentiviral vectors, circular RNA and targeted delivery technologies.

The strategic question is therefore changing.

Is in vivo CAR-T simply a faster version of existing cell therapy, or could it create an entirely different operating model for cell therapy?

What Is In Vivo CAR-T Therapy?

Traditional CAR-T therapy is an ex vivo process.

A patient’s T cells are collected through apheresis and transported to a manufacturing facility. The cells are genetically modified to express a chimeric antigen receptor, expanded, tested and returned to the patient after appropriate preparation.

This approach has transformed treatment for several blood cancers, but it also creates significant manufacturing and logistical requirements.

In vivo CAR-T takes a different approach.

The therapeutic product is designed to deliver genetic instructions directly to selected immune cells inside the patient’s body. These cells are then programmed to express a CAR and perform the intended therapeutic function.

The simplified model becomes:

Ex vivo CAR-T

Patient → Cell collection → Genetic engineering → Cell expansion → Quality testing → Reinfusion

In vivo CAR-T

Patient → Targeted delivery → Immune-cell engineering inside the body → CAR-T generation

This difference could have major implications for treatment time, manufacturing capacity, supply chains and patient access.

Umoja Biopharma, for example, describes its VivoVec platform as a system designed to generate CAR-T cells directly in the patient, potentially eliminating the weeks-to-months manufacturing timeline associated with conventional ex vivo CAR-T.

Why Is Big Pharma Investing Billions in In Vivo CAR-T?

The commercial interest is difficult to ignore.

The sector has attracted a series of major acquisitions and partnerships involving some of the world’s largest pharmaceutical companies.

AbbVie and Capstan Therapeutics

AbbVie completed its acquisition of Capstan Therapeutics in August 2025.

The transaction added Capstan’s targeted lipid nanoparticle platform and CPTX2309, a Phase 1 in vivo CD19 CAR-T program focused on B-cell-mediated autoimmune diseases. The platform is designed to use targeted LNPs to generate CD19-specific CAR-T cells inside the body.

The transaction was valued at approximately $2.1 billion.

AstraZeneca and EsoBiotec

AstraZeneca completed its acquisition of EsoBiotec in May 2025 for up to $1 billion.

EsoBiotec’s ENaBL platform uses targeted lentiviral vectors to deliver genetic instructions to immune cells. Its technology is being developed for cancer and potentially immune-mediated diseases.

Gilead/Kite and Interius BioTherapeutics

Kite, a Gilead company, agreed to acquire Interius BioTherapeutics for $350 million.

Interius’s platform is designed to generate CAR-T cells directly inside the patient through an in vivo lentiviral approach. Its lead program INT2104 targets CD20 and has been developed for B-cell malignancies.

Bristol Myers Squibb and Orbital Therapeutics

Bristol Myers Squibb agreed to acquire Orbital Therapeutics for $1.5 billion.

Orbital’s OTX-201 is an investigational in vivo CAR-T approach using circular RNA and targeted lipid nanoparticles to generate a CD19-directed CAR inside the body. The initial focus is autoimmune disease.

Eli Lilly and Orna Therapeutics

In February 2026, Eli Lilly announced its agreement to acquire Orna Therapeutics.

Orna’s platform combines engineered circular RNA with lipid nanoparticles. Its lead program, ORN-252, is a CD19-targeting in vivo CAR-T therapy designed for B-cell-driven autoimmune diseases.

The transaction could provide Orna shareholders with up to $2.4 billion, including upfront and milestone payments.

Eli Lilly and Kelonia Therapeutics

Lilly then announced another major move in April 2026 by agreeing to acquire Kelonia Therapeutics.

Kelonia’s lead program, KLN-1010, is a Phase 1 lentiviral in vivo CAR-T therapy for relapsed/refractory multiple myeloma. Its iGPS technology is designed to selectively deliver genetic material to T cells inside the body.

The transaction could reach $7 billion, including an upfront payment of $3.25 billion and potential development, regulatory and commercial milestones.

This is important because the competitive landscape is no longer being defined only by individual CAR-T candidates.

Pharma companies are acquiring the underlying platforms.

That suggests the strategic value may sit not only in the final therapy but also in the delivery technology, genetic engineering system and ability to build multiple future therapies from the same platform.

Who Is Building the In Vivo CAR-T Landscape?

The competitive landscape is becoming increasingly diversified.

Company	Strategic Partner/Owner	Approach	Key Focus
Capstan Therapeutics	AbbVie	Targeted LNP	CD19 CAR-T, autoimmune disease
Interius BioTherapeutics	Gilead/Kite	Lentiviral delivery	CD20, B-cell malignancies
EsoBiotec	AstraZeneca	Targeted lentiviral ENaBL	BCMA, multiple myeloma
Umoja Biopharma	AbbVie collaboration	VivoVec lentiviral platform	B-cell malignancies
Orna Therapeutics	Eli Lilly	Circular RNA + LNP	CD19, autoimmune disease
Kelonia Therapeutics	Eli Lilly	Lentiviral iGPS	BCMA, multiple myeloma
Orbital Therapeutics	Bristol Myers Squibb	Circular RNA + targeted LNP	CD19, autoimmune disease
Kelonia, Capstan and other emerging platforms	Major pharma	Multiple delivery approaches	Oncology and autoimmune disease

The landscape is not converging around one technology.

Instead, companies are testing different combinations of:

• Lentiviral vectors
• Lipid nanoparticles
• Circular RNA
• mRNA
• Targeted antibodies
• Cell-specific delivery
• Transient and persistent expression
• Different CAR targets

A 2026 review of the translational landscape similarly identifies multiple clinical-stage approaches using different delivery vehicles and targets, highlighting how early and technically diverse the field remains.

Why Are Autoimmune Diseases Becoming a Major Target?

One of the most interesting developments is that in vivo CAR-T is not being developed only for cancer.

Several major programs are focused on B-cell-driven autoimmune diseases.

The underlying rationale is connected to the ability of CAR-T cells to eliminate specific B-cell populations and potentially reset dysfunctional immune responses.

For developers, an in vivo approach could theoretically reduce some of the complexity associated with manufacturing a separate cellular product for every patient.

This creates a potentially attractive commercial proposition:

Instead of building a personalized cell product outside the body, could a standardized drug product program a patient’s immune system inside the body?

That distinction could influence:

• Treatment-center requirements
• Manufacturing capacity
• Patient eligibility
• Treatment turnaround time
• Supply-chain requirements
• Cost structure
• Geographic accessibility
• Hospital infrastructure
• Reimbursement models

However, these are potential advantages, not established clinical or economic outcomes. The field still needs clinical evidence demonstrating that in vivo approaches can match the efficacy, durability and safety of established CAR-T therapies.

The Biggest Challenge Is Not Simply Delivery

It is tempting to describe in vivo CAR-T as a manufacturing breakthrough.

But manufacturing is only one part of the equation.

The bigger scientific challenge is control.

A successful platform needs to answer several questions.

1. Which cells receive the genetic payload?

Targeting the correct immune-cell population is fundamental.

A delivery system that reaches unintended cells could create safety problems or reduce therapeutic effectiveness.

2. How much CAR-T generation is enough?

The therapeutic effect depends on generating an adequate population of functional CAR-expressing cells.

Too little activity could reduce efficacy.

Too much activity could potentially increase toxicity.

3. How long should CAR expression last?

Different platforms are exploring different strategies for genetic expression.

RNA-based approaches can provide transient expression, while integrating viral approaches may provide longer-lasting genetic modification.

The optimal balance between persistence and controllability remains an important development question.

4. Can the process be stopped?

This is one of the most important questions for developers.

With a manufactured CAR-T product, the cellular product can be extensively characterized before administration.

With in vivo engineering, the therapeutic process begins inside the patient.

That places greater importance on targeting specificity, dose control, vector design, pharmacology and safety mechanisms.

5. Can the platform be repeated?

A commercially important question is whether patients could receive additional treatment if needed.

Repeat dosing may depend on the delivery vehicle, immune response to the vector, persistence of engineered cells and the biological characteristics of the therapy.

LNP vs Lentiviral Vectors: Which Technology Will Win?

There is currently no obvious winner.

Targeted LNP approaches

LNP-based systems can deliver RNA payloads and potentially provide transient cellular programming.

Capstan, Orna and Orbital have pursued approaches involving targeted LNPs and RNA technologies.

Potential advantages include:

• RNA-based programming
• Transient expression
• Flexible payload engineering
• Potential platform scalability
• Compatibility with targeted delivery strategies

Lentiviral approaches

Lentiviral platforms are being used by companies including Interius, EsoBiotec, Umoja and Kelonia.

These approaches aim to deliver genetic instructions directly to immune cells in vivo, with some platforms designed to provide persistent genetic modification.

Potential advantages include:

• Longer-lasting expression
• Established viral-vector engineering knowledge
• Potentially durable CAR-T generation
• Applicability to multiple therapeutic targets

But persistence also raises an important question:

Does greater durability necessarily mean greater clinical value if controllability becomes more difficult?

That question could become one of the defining competitive dimensions of the category.

What Does In Vivo CAR-T Mean for Manufacturing?

This could be one of the most significant changes.

Traditional CAR-T requires a complex manufacturing ecosystem involving:

• Cell collection
• Patient-specific manufacturing
• Viral or nonviral gene transfer
• Cell expansion
• Quality control
• Cryopreservation
• Logistics
• Chain-of-identity systems
• Specialized treatment centers

In vivo CAR-T aims to shift much of that complexity toward drug-like manufacturing and delivery.

The manufacturing model could potentially become closer to:

Manufacture standardized therapeutic product → distribute → administer → generate therapeutic cells in the patient

If clinical development validates this model, the implications for cell therapy CDMOs, logistics providers, hospitals and treatment centers could be significant.

It could also change the competitive landscape for companies providing:

• Viral-vector manufacturing
• LNP manufacturing
• RNA manufacturing
• Analytical testing
• Fill-finish
• Cold-chain logistics
• Cell therapy infrastructure
• Quality and regulatory services

But In Vivo CAR-T Does Not Automatically Mean Lower Cost

This distinction matters for investors and commercial teams.

Removing patient-specific cell manufacturing does not automatically eliminate all costs.

Developers still need to address:

• Vector or LNP production
• Raw materials
• Quality control
• Potency assays
• Stability
• Distribution
• Patient monitoring
• Hospital administration
• Adverse-event management
• Long-term follow-up
• Regulatory requirements

The commercial question is therefore not simply:

“Is in vivo CAR-T cheaper?”

It is:

“Can the complete treatment pathway become sufficiently simpler and scalable to improve the economics of cell therapy?”

That requires evidence.

What Could In Vivo CAR-T Mean for Cancer Treatment?

The first clinical opportunities are heavily concentrated around diseases where CAR-T biology is already validated.

B-cell malignancies and multiple myeloma are therefore logical starting points.

Umoja received FDA clearance for its IND application for UB-VV400 in July 2026. The CD22-directed in vivo CAR-T candidate is being developed for adults with relapsed/refractory B-cell malignancies, with the company expecting the first patient to be dosed in the third quarter of 2026.

Kelonia’s KLN-1010 is another important program, with Phase 1 development focused on relapsed/refractory multiple myeloma.

The larger long-term question is whether the technology can expand beyond these initial indications.

Solid tumors remain a harder challenge

In vivo CAR-T does not automatically solve the biological challenges associated with solid tumors.

Developers still need to address:

• Tumor antigen heterogeneity
• Tumor penetration
• Immunosuppressive microenvironments
• Antigen escape
• CAR-T persistence
• On-target/off-tumor toxicity

Therefore, the commercial potential of in vivo CAR-T should not be judged solely by how quickly the technology can reproduce existing hematological CAR-T approaches.

The bigger upside could come if platform technologies eventually demonstrate meaningful activity across multiple disease classes.

The Investment Story Is Becoming a Platform Story

The acquisition activity tells us something important.

Pharma companies are not simply buying individual molecules.

They are buying platforms.

• AbbVie acquired Capstan.
• AstraZeneca acquired EsoBiotec.
• Gilead/Kite acquired Interius.
• BMS acquired Orbital.
• Lilly moved into the field through Orna and Kelonia.

These transactions demonstrate a strategic race around the underlying technologies required to engineer immune cells inside the body.

For investors and business-development teams, this creates a different competitive-intelligence question:

Which platform can generate multiple commercially valuable therapies rather than only one successful CAR-T program?

What Should Pharma and Biotech Companies Track in 2026?

For companies evaluating this space, several indicators deserve close monitoring.

Clinical differentiation

Watch:

• Response rates
• Complete response rates
• Duration of response
• Minimal residual disease
• CAR-T persistence
• B-cell depletion
• Safety signals
• Cytokine release syndrome
• Neurological toxicity
• Repeat dosing potential

Platform differentiation

Compare:

• Delivery specificity
• Payload capacity
• RNA vs DNA approaches
• Transient vs persistent expression
• Vector immunogenicity
• Target-cell selectivity
• Manufacturing complexity

Commercial differentiation

Assess:

• Treatment-center requirements
• Product availability
• Cost of goods
• Administration requirements
• Patient throughput
• Reimbursement potential
• Geographic scalability

Business-development activity

Track:

• Licensing agreements
• Acquisitions
• Option deals
• Strategic collaborations
• Platform partnerships
• CDMO agreements
• New indications

What Does This Mean for Healthcare Decision-Makers?

The opportunity around in vivo CAR-T extends beyond drug developers.

For pharma companies

The strategic question is whether to:

Build, buy or partner.

Internal platform development may offer greater control, while acquisitions can accelerate access to validated technologies and scientific teams.

For biotech companies

The key question is:

Does the platform have value beyond one lead asset?

A strong delivery platform with multiple therapeutic applications may attract significantly greater partnering interest.

For CDMOs

The manufacturing opportunity could shift toward:

• RNA production
• LNP formulation
• Viral-vector manufacturing
• Analytical development
• Drug-product manufacturing
• Specialized delivery systems

For investors

The most important distinction is between:

scientific promise and clinical validation.

A large acquisition price demonstrates strategic interest. It does not establish clinical efficacy.

The next valuation inflection points will increasingly come from human clinical data.

How Towards Healthcare Research & Consulting Can Support In Vivo CAR-T Strategy

The rapid development of in vivo CAR-T is creating a fragmented intelligence environment.

Scientific publications explain the technology.

Clinical-trial databases show development progress.

Company announcements reveal partnerships.

Patent filings reveal competitive positioning.

But decision-makers need these pieces connected.

Towards Healthcare Research & Consulting can support companies evaluating this emerging category through:

Competitive Intelligence

Benchmark companies, platforms, lead candidates, targets, clinical stages and strategic positioning.

Pipeline Intelligence

Track emerging in vivo CAR-T programs from preclinical development through clinical trials, regulatory milestones and data readouts.

Technology Benchmarking

Compare LNP, lentiviral, RNA, circular RNA and other delivery approaches across targeting, persistence, safety and development maturity.

TAM, SAM and SOM Analysis

Assess the commercial opportunity across oncology and autoimmune indications using a bottom-up approach based on patient populations, treatment pathways, pricing assumptions and adoption scenarios.

Buyer Intelligence

Identify pharmaceutical, biotech, CDMO, hospital and healthcare-system stakeholders that could influence adoption.

Partnership and M&A Intelligence

Track licensing agreements, acquisitions, platform collaborations and potential strategic targets.

Patent and IP Intelligence

Map technology ownership, delivery platforms, CAR constructs, genetic engineering approaches and competitive patent activity.

Manufacturing Intelligence

Assess the implications for viral-vector, RNA, LNP, analytical and cell-therapy manufacturing ecosystems.

Go-to-Market Strategy

Evaluate treatment pathways, customer segments, competitive positioning, reimbursement considerations and launch opportunities.

The objective is not simply to provide information.

It is to convert fragmented scientific and commercial data into decision-ready intelligence.

The Bigger Question: Are We Changing How Cell Therapy Is Made?

The most important development in in vivo CAR-T may not be a single product.

It may be the change in the underlying manufacturing philosophy.

Traditional CAR-T asks:

How can we manufacture the right therapeutic cells for each patient?

In vivo CAR-T asks:

How can we program the patient’s own cells to become the therapy?

That is a fundamentally different approach.

But calling it a revolution today would be premature.

The technology still needs to demonstrate:

• Reliable cell targeting
• Predictable CAR expression
• Durable clinical responses
• Acceptable safety
• Reproducible manufacturing
• Scalable delivery
• Commercial viability

The first clinical programs will provide the evidence needed to determine whether the industry’s multibillion-dollar investment is justified.