In May, at the annual meeting of the American Society of Gene & Cell Therapy (ASGCT), long lines formed outside a session dedicated to in vivo CAR-T.

 

At this year's ASGCT, over 50 abstracts were related to in vivo CAR-T, the excitement nearly drowning out other topics. Yet beneath the enthusiasm, skepticism was equally audible. One researcher used a blunt word – "bubble" – to describe the field outside the session hall. A company executive commented that while "bright spots in new designs" were seen this year, "there are many me-too programs with only minor differences from each other." Importantly, nearly all the data still came from mice and non-human primates.

 

Just one month earlier, at the American Association for Cancer Research (AACR) annual meeting, the in vivo CAR-T field had a landmark moment. Kelonia Therapeutics presented Phase I clinical data for its BCMA-targeted in vivo CAR-T candidate, KLN-1010: four patients all achieved MRD negativity, with the longest maintaining complete remission for five months; in vivo CAR-Ts comprised up to 85% of circulating T cells, with memory cell persistence at three months; no Grade 3 or higher CRS occurred, and no lymphodepletion was required. Around the same time, Eli Lilly announced its acquisition of Kelonia for up to US$7 billion.

 

Two meetings, two different sentiments.

 

In 2026, the in vivo CAR-T field stands exactly at the intersection of "bubble" and "proof." And here, the names of Chinese biotech companies are impossible to ignore.

 

TONACEA 01: Why "In Vivo"?

 

To understand the value of in vivo CAR-T, one must first understand the manufacturing challenges of traditional autologous CAR-T. Over the past decade, autologous CAR-T has been well-validated in hematologic malignancies, with over ten products approved globally. According to a Fortune Business Insights report, cumulative sales in 2025 approached US$9 billion. Yet the gap between "works well" and "broadly accessible" has never been fully closed.

 

The manufacturing process for conventional CAR-T is highly individualized: T cells are collected from the patient, genetically modified and expanded ex vivo, then reinfused into the patient. Before reinfusion, patients receive lymphodepleting chemotherapy. The entire process takes 2 to 4 weeks, with high manufacturing costs reflected in list prices of US370,000tooverUS370,000tooverUS500,000 per infusion in the US, and approximately RMB 1 million in China. Lymphodepletion itself also carries risks of infection and hematopoietic suppression.

 

In vivo CAR-T attempts to rewrite this logic. Using gene delivery vectors, it reprograms T cells directly inside the patient's body, eliminating ex vivo manufacturing and the need for lymphodepletion. The commercial upside is that manufacturing costs could potentially fall to less than one-fifth of traditional CAR-T. Treatment could shift from inpatient centers in leading tertiary hospitals to outpatient settings. Cell therapy accessibility could move from "million-yuan level" toward "broad affordability."

 

Current competition centers on two main delivery technology routes.

 

The first is the lentiviral vector route, which integrates the CAR gene into the T cell genome, pursuing a single-dose, durable response. Kelonia's KLN-1010 and Immvira's IMV102 belong to this camp.

 

The second is the LNP/mRNA route, which uses lipid nanoparticles to deliver mRNA or circular RNA encoding the CAR, achieving transient expression in T cells. Its advantages include no risk of genomic integration, higher safety, and the potential for repeat dosing, making it suitable for indications such as autoimmune diseases where fine control over the therapeutic window is needed. Micro-Tao Bio (spun out of GRIT Biotechnology) and Capstan Therapeutics are among those betting on the LNP route.

 

Neither route is inherently superior; they are better suited to different indications and clinical needs. The lentiviral route aligns more closely with the "one-time cure" treatment paradigm for hematologic malignancies, while the LNP route offers greater differentiation in autoimmune diseases. A third route, using AAV vectors combined with site-specific integration, is also being explored, with Azalea Therapeutics as a representative.

 

TONACEA 02: What Are MNCs Buying?

 

Since 2025, MNC activity in the in vivo CAR-T field can no longer be described as "strategic positioning." A more accurate term is "staking a claim."

 

AbbVie acquired Capstan Therapeutics for up to US2.1billion;AstraZenecaacquiredEsoBiotec;BMSacquiredOrbitalTherapeuticsforUS2.1billion;AstraZenecaacquiredEsoBiotec;BMSacquiredOrbitalTherapeuticsforUS1.5 billion; Kite, a Gilead company, announced a collaboration with Pregene Biopharma worth up to US1.6billion.ThencameEliLilly,pushingthewavetoanewlevel:inFebruary2026,itacquiredOrnaTherapeuticsforuptoUS1.6billion.ThencameEliLilly,pushingthewavetoanewlevel:inFebruary2026,itacquiredOrnaTherapeuticsforuptoUS2.4 billion (LNP-oRNA route); in April, it acquired Kelonia for up to US7billion.Lilly′scumulativeinvestmentintheinvivoCAR−TfieldisnowclosetoUS7billion.Lilly′scumulativeinvestmentintheinvivoCAR−TfieldisnowclosetoUS10 billion.

 

Lilly's upfront payment for Kelonia was US3.25billion,withuptoUS3.25billion,withuptoUS3.75 billion in milestones – a valuation far exceeding market expectations. Before the deal was announced, industry consensus was around US2billion.AccordingtoPitchBookdata,Kelonia′svaluationin2022wasjustoverUS2billion.AccordingtoPitchBookdata,Kelonia′svaluationin2022wasjustoverUS100 million. An almost 70-fold increase in four years, with the core driver being clinical data.

 

The 100% MRD negativity rate, memory cell persistence signal, and favorable safety profile of KLN-1010, combined with its IND clearance from the FDA in January 2026 (making it the first anti-BCMA in vivo CAR-T to initiate a multi-center clinical trial in the US), together justified Lilly's heavy bet.

 

Not all large pharma are chasing this target, however. Novartis CEO Vas Narasimhan stated on the company's Q1 2026 earnings call that the company continues to evaluate the in vivo CAR-T space but has no specific acquisition plans at present. He also emphasized confidence in Novartis's own immune-reset portfolio: its autologous CD19 CAR-T, rapcabtagene autoleucel, is in Phase II studies for autoimmune indications such as lupus nephritis, with a planned BLA submission in 2028.

 

With the acquisition of Kelonia, Capstan, Orbital, EsoBiotec, and others, the number of independent, available in vivo CAR-T companies in the market is diminishing. A PitchBook analyst noted that large pharma companies without in vivo CAR-T programs currently include Johnson & Johnson and Novartis. A Donghai Securities report also concluded that four overseas in vivo CAR-T companies in the first tier of global clinical development have all been acquired except for Umoja, and that "the scarcity of assets has significantly increased."

 

TONACEA 03: The Eastern Contingent

 

Beyond the capital feast of international giants, Chinese biotechs are quietly assembling on the in vivo CAR-T track. Data from Dingxiangyuan Insight shows over 180 in vivo CAR-T pipelines globally, with approximately half originating from China.

 

The 2026 AACR annual meeting served as a concentrated showcase for China's in vivo CAR-T capabilities. Immvira Biotech, Micro-Tao Bio/GRIT Biotechnology, Westlake University, and other institutions presented multiple studies, with targets covering mature hematologic targets such as BCMA and CD19, as well as extending to new directions like DLL3 (small cell lung cancer) and CD13 (acute myeloid leukemia). Delivery strategies encompassed lentiviral vectors, T-cell-targeted LNPs, erythrocyte-mediated delivery, and circular RNA.

 

Immvira presented preclinical data for IMV102, its BCMA-targeted in vivo CAR-T candidate developed on its proprietary iMAGIC platform. This platform uses modified lentiviral vectors, with a mutant MxV glycoprotein on the surface to eliminate non-specific receptor binding, while incorporating a T-cell-targeting module (TCM3) for high-specificity T cell transduction. Data showed that IMV102 achieved significant and sustained tumor burden reduction in two multiple myeloma xenograft mouse models, with efficient transduction in T cells but no detectable transduction in non-target cells such as hepatocytes. The company has built a dual-engine model with both ex vivo and in vivo CAR-T platforms. Its autologous solid tumor CAR-T pipeline, IMC002, has entered Phase III clinical trials in China. Its in vivo CAR-T pipeline covers hematologic malignancies, solid tumors, and autoimmune diseases, with IMV101 (CD19-targeted) having entered IIT. In March 2026, the company completed a nearly RMB 200 million pre-IPO financing round, raising over RMB 600 million in total within a year.

 

Micro-Tao Bio/GRIT Biotechnology presented GT801, a CD19-targeted in vivo CAR-T candidate based on a T-cell-targeted LNP platform. This product uses the CLAMP platform to conjugate VHH nanobodies to the LNP surface, enabling selective uptake by T cells, and encapsulates chemically modified mRNA encoding CD19 CAR. Preclinical data showed that a single intravenous dose of 0.01 mg/kg cleared over 95% of B cells, and a 0.1 mg/kg dose achieved near-complete B cell clearance across multiple lymphoid tissues. More importantly, GT801 has reported preliminary human data, validating in vivo CAR expression and the feasibility of repeat dosing, while exhibiting very low cytokine release levels on safety.

 

From a broader perspective, Chinese teams are demonstrating noteworthy diversity in delivery technology. Westlake University presented its mRNA-LNP-Ery platform, which leverages the spleen-homing ability of erythrocytes to deliver mRNA, generating CAR-myeloid cells in the spleen to reshape the tumor immune microenvironment in solid tumors. Several teams are using circular RNA as an expression vector to extend the expression window and reduce immunogenicity, a direction where China could develop a comparative advantage in the in vivo CAR-T field.

 

However, it must be noted that the vast majority of Chinese pipelines remain in preclinical or very early-stage clinical exploration. CSPC Pharmaceutical's SYS6055 has become the first in vivo CAR-T product to enter clinical trials in China. However, the overall pace of translation from preclinical to registrational clinical development in China still lags behind the top international tier.

 

Final Thoughts

 

As industry attention focuses on clinical data and acquisition values, some questions remain unanswered. Kelonia's detection of memory cell persistence at the 3-month follow-up is certainly positive, but proving durability comparable to traditional CAR-T's multi-year persistence remains a longer-term question. The risk of insertional mutagenesis with the lentiviral route needs longer follow-up to exclude. For the LNP/mRNA route, transient expression depends on repeat dosing; immunogenicity and long-term efficacy lack clinical data support.

 

In solid tumors, while explorations such as KIR-CAR and multi-immune cell engineering appeared at the 2026 AACR meeting, systemic challenges including microenvironmental suppression, insufficient T cell infiltration, and antigen heterogeneity will not automatically disappear simply because the delivery method shifts from ex vivo to in vivo. The approach of CREATE Medicines – simultaneously engineering T, NK, and myeloid cells – is therefore noteworthy, representing a direction for breaking the deadlock from the microenvironment level.

 

Regulation is also lagging. The FDA has indicated it is reviewing a draft of "reasonable mechanism pathways" to accelerate personalized drug development but emphasizes this is a "living framework," not an approval pathway. For the entirely new paradigm of in vivo CAR-T, there is not yet a mature review template.

 

2026 is a turning point year for in vivo CAR-T, moving from "proof-of-concept" toward "clinical validation." The fundamental question this technology still needs to answer is simple: can it achieve or surpass the durability and safety of traditional CAR-T while delivering on the promise of accessibility? The answer to that question may not need to wait very long.

 

References:

1. Novartis CEO 'continuing to evaluate' in vivo CAR-Ts, but no deals in the works; Fierce Pharma

2. ASGCT dispatch: In vivo CAR-T is everywhere; Endpoints

3. In Vivo CAR-T: A Scarcity of Targets?; TONACEA