In Vivo CAR-T2026-07-16

In Vivo CAR-T Landscape: T-cell Reprogramming Directly in Patients

Advances in drug delivery and RNA modification have made in vivo programming of T-cells possible. Here is where the in vivo CAR-T pipeline stands today.

History of CAR-T Therapy

Chimeric Antigen Receptor T-Cell (CAR-T) therapy has continued to offer promising outcomes in cancer and other disease areas. The first traditional CAR-T therapy (Kymriah) was FDA approved in 2017, and while it boasted promising results for leukemia patients, the therapy came with numerous drawbacks.^[1] This included a $500,000 price tag, a burdensome lymphodepletion cycle just to be able to receive the therapy, and a patient-by-patient bespoke in vitro cell-engineering process that took weeks.^[2]^[3]^[4] Kymriah itself still takes 3-4 weeks between patient cell harvesting and drug infusion, which can be critical weeks for a late-stage cancer patient.^[5]

Off-the-shelf allogeneic CAR-Ts were another approach attempting to overcome the scaling limitations of autologous CAR-T therapy. Allogeneic CAR-T however also posed major immune system complications, namely graft-versus-host and host-versus-graft disease where either the foreign cells attack the patient or the patient's immune system kills the foreign CAR-Ts.^[6]

Further innovation was needed if CAR-T was going to become a globally accessible and affordable treatment.

Recently, advancements have been made enabling in vivo CAR-T therapies to become a reality. Rather than having to harvest T-cells from the patient and transduce them with CARs in a lab, in vivo therapy involves delivery of CAR genetic material into the patient's body, using targeted delivery vectors that find and reprogram the patient's T-cells, generating CAR-Ts all while the cells remain in the patient's body.^[7] This bypasses a lot of the limitations of traditional in vitro CAR-T therapies, including the slow CAR-T engineering process, unscalable manufacturing, and associated high costs.

Therapeutic Approaches & Targets

Innovation in development of in vivo CAR-T therapy has led to bifurcation of therapeutic strategy into permanent CAR-T generation versus temporary / transient expression:

1 Permanent CAR-T Expression

Mechanism: The most common approach for permanent CAR-T expression involves delivery of RNA material encoding the chimeric antigen receptor using a modified lentiviral delivery vector. The lentiviral surface has proteins targeting T-cells (most often CD4+ and CD8+) for steering in the body, and contains the necessary machinery to embed the CAR genetic material into the T-cell's DNA for expression.

Target Disease: Most often, permanent CAR-T expression is being used to target oncology indications since achieving a clinical response and preventing relapse of disease requires robust, durable, and continuous CAR-T cell surveillance in the body.

2 Transient CAR-T Expression

Mechanism: The most common approach for transient CAR-T expression involves delivery of mRNA material that does not make it to the cell's nucleus and is instead directly translated into protein and expressed in the cell temporarily, as mRNA is eventually degraded within the cell. Because the CAR genetic material is not permanently encoded into the T-cell's DNA, the CARs are only expressed temporarily on the T-cell's surface.

Target Disease: Transient CAR-T expression is primarily being developed to treat autoimmune conditions as temporary deletion of B cells is more advantageous, allowing the immune system to reset and rebuild healthy B-cells after treatment.

Here is a side-by-side comparison of the general approach to permanent and transient CAR-T expression. These characteristics are the norm but most definitely not hard and fast rules:

Characteristic	Permanent	Transient
Delivery Vector	Modified lentivirus	Targeted lipid nanoparticle (TLNP)
Drug Payload	RNA	mRNA
Molecular Targets	CD19, BCMA, GPRC5D, CD20, CD22	CD19, BCMA, TROP2, GPC3, HER2
Target Disease Area	Oncology	Autoimmune Disease

A few biotechs are pursuing unique strategies that further enhance these two common approaches. Below are some of the more promising advancements:

1 Circular mRNA Payload

Spearheaded by Oran Therapeutics (acquired by Eli Lilly), circular mRNA can persist in the cell's cytoplasm for longer, enabling longer expression of CAR in T-cells while still retaining the transient property.^[8] This may yield more effective in vivo CAR-T treatments that also require less frequent dosing for patients.

2 Rapamycin-Controlled Expression Knob

Umoja Biopharma has developed a unique component that is programmed into T-cells alongside the CAR that enables modulation of CAR-T cell counts in the body. A rapamycin cytokine receptor is included in the payload and programmed into the T-cells alongside the CAR, so that when patients take the drug rapamycin, this not only promotes increased expression of CAR-T in the body, but through rapamycin's properties also suppresses regular T-cells that may interfere with the therapeutic effects of CAR-T. Umoja has essentially added a 'CAR-T volume intensity' knob that can be controlled with a pill as the dial.

3 Targeting Immune Cells Other Than T-Cells

Many biotechs are developing CAR therapeutics that target myeloid cells and natural killer (NK) cells, either in place of or in addition to T-cells. These present additional layers of therapy that can be supplemental to the more traditional in vivo CAR-Ts being developed, helping mount a more reinforced immune system attack on the disease.

4 Permanent Expression via TLNP

What may be the most promising advancement for in vivo CAR-T is the use of TLNPs instead of lentiviral vectors to deliver CAR RNA for permanent CAR-T expression. Lentiviruses are currently used for permanent CAR-T largely due to their highly effective gene insertion mechanism. However, LNPs are more advantageous as a delivery vector since they are much easier to manufacture with quality and at scale. Biotechs like CREATE Medicines are developing LNP delivery platforms that also contain the machinery necessary for permanent insertion of DNA into T-cells, paving the road for even more scalable and effective in vivo CAR-T therapies.

Incremental innovation will continue to pop up in the in vivo CAR-T space, driving further enhancements to safety, dosing, convenience, and most importantly therapeutic effect.

Pipeline Overview

The in vivo CAR-T pipeline is still very young, with no approved therapies on the market and furthest along clinical stage trials in phase 1. This is in part due to the relatively long phase 1 trials that need to be conducted to assess the safety of an immunotherapy as well as the long-term effects of delivering a genetic medicine. Furthermore, most of these assets are going after extremely high unmet need oncology indications, often for multiple relapsed/refractory patient populations, meaning that they can likely pursue FDA approval after a phase 2 and would not require extensive phase 3 testing. In other words, the pipeline is further along in development than it may seem.

Some summary statistics on the major in vivo CAR-T pipeline assets covered in this report:

There is an even split of 7 assets each for transient and permanent CAR-T expression therapeutic approaches
4 of the 10 distinct companies are US-based, another 4 Chinese, 1 a US/China-based hybrid, and 1 EU-based pharma

Below is a timeline of the top 14 assets in development:

In Vivo CAR-T Clinical Development Timeline

2023 2024 2025 2026 2027 2028 2029 2030 Today

UB-VV111Umoja Biopharma

UB-VV400Umoja Biopharma

KLN-1010Eli Lilly

ESO-T01AstraZeneca

LB2501Legend Biotech

INT2104Kite/Gilead

CPTX2309AbbVie

HN2301MagicRNA

ORN-252Eli Lilly

MT-302CREATE Medicines

JCXH-213Immorna

STR-P004Starna

INVICTA-1 (NCT06528301)

Phase 1

NCT06743503

Phase 1 (China only)

inMMyCAR (NCT07075185)

Phase 1

NCT06791681

Phase 1 (China only)

NCT07002112

Phase 1 (China only)

INVISE (NCT06539338)

Phase 1

NCT06917742

Phase 1

NCT06801119

Phase 1

NCT07439796

Phase 1

MYE-Symphony (NCT05969041)

Phase 1

NCT06618313

Phase 1

NCT07143617

Pre-Phase 1 (exploratory)

Permanent CAR expression Transient CAR expression Pre-Phase 1 / exploratory

Note: The estimated trial start and completion dates are derived from clinicaltrials.gov. Most trial completion dates are projections and can often be overestimates. CRT-402 and CRT-403 (CREATE Medicines) are excluded from the timeline above as both remain preclinical with no disclosed trial dates.

Below is a summary of the top 14 programs in development:

In vivo CAR-T pipeline summary available as a spreadsheet.

Drug Name	Strategy	Delivery Vector	Payload	Sponsor(s)	Sponsor Country	Phase
UB-VV111	Permanent	Modified lentivirus	anti-CD19 CAR RNA + rapamycin-activated cytokine receptor	Umoja Biopharma, AbbVie	US	Phase 1
UB-VV400	Permanent	Modified lentivirus	anti-CD22 CAR RNA + rapamycin-activated cytokine receptor	Umoja Biopharma, Nanjing IASO Biotechnology	US, China	Phase 1
KLN-1010	Permanent	Modified lentivirus	anti-BCMA CAR transgene	Eli Lilly	US	Phase 1
ESO-T01	Permanent	Modified lentivirus	anti-BCMA CAR transgene	AstraZeneca, EsoBiotec	UK, Belgium	Phase 1
LB2501	Permanent	Modified lentivirus	anti-CD19/CD20 dual-targeting CAR transgene	Legend Biotech	US/China Hybrid	Phase 1
INT2104	Permanent	Modified lentivirus (T-cell and NK-cell transduction)	anti-CD20 CAR transgene	Kite Pharma (Gilead)	US	Phase 1
CPTX2309	Transient	Targeted lipid nanoparticle	anti-CD19 CAR mRNA	AbbVie (Capstan Therapeutics)	US	Phase 1
HN2301	Transient	Targeted lipid nanoparticle	anti-CD19 CAR mRNA	Shenzhen MagicRNA Biotechnology	China	Phase 1
ORN-252	Transient	Targeted lipid nanoparticle	anti-CD19 CAR circular mRNA	Eli Lilly (Orna Therapeutics)	US	Phase 1
MT-302	Transient	Targeted lipid nanoparticle (myeloid cell transduction)	anti-TROP2 CAR mRNA	CREATE Medicines	US	Phase 1
JCXH-213	Transient	Targeted lipid nanoparticle	anti-CD19 CAR mRNA	Immorna	China	Phase 1
STR-P004	Transient	Targeted lipid nanoparticle	anti-CD19 CAR mRNA	Starna Therapeutics	China	Pre-Phase 1 (exploratory)
CRT-402	Transient	Targeted lipid nanoparticle	anti-CD19 CAR mRNA	CREATE Medicines	US	Preclinical
CRT-403	Permanent	Targeted lipid nanoparticle (RetroT platform)	anti-CD19/BCMA dual-CAR RNA	CREATE Medicines	US	Preclinical

Pipeline Coverage Disclaimer: While this report is intended to be comprehensive of the global in vivo CAR-T drug development pipeline, it does not cover every asset. Highest coverage priority is on assets in later stages of clinical development. Assets in preclinical and discovery stages are also included to the extent possible, but were deprioritized as they are currently less consequential to the in vivo CAR-T treatment landscape. Furthermore, assets from Chinese biotechs tend to have much smaller digital footprints and may not have all been captured.

Pipeline Deep Dive

1. UB-VV111 (Umoja Biopharma)

Name(s)	UB-VV111
Therapeutic Strategy	Permanent CAR expression
Delivery Vector	Modified lentivirus^[9]
Payload	Anti-CD19 CAR transgene; Rapamycin Activated Cytokine Receptor (selective growth switch for CAR-T cells in the body and suppression of other T cells)^[9]
Lead Indication	Relapsed/Refractory CD19+ B-cell Malignancies (including Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia)^[10]^[9]
ROA	Intravenous or Intranodal (i.e., directly into a lymph node)^[11]
Sponsor(s)	Umoja Biopharma, AbbVie (partnership between the two sponsors; AbbVie does not own the rights to UB-VV111 but has the option to license it)^[12]
Sponsor Country	US (both)
Trial Name / NCT ID	INVICTA-1 (NCT06528301)^[10]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

The most recent update came in 2025 when Umoja announced FDA Fast Track Designation for the therapy.^[13] The study itself is still recruiting and is slated to kick off soon, with expected completion as far as 2029 (although clinicaltrials.gov estimates can often be inaccurate).^[10]

Competitive Advantage / Bold Bet

The therapy is being delivered alongside a rapamycin receptor, allowing the use of the additional therapy rapamycin to bolster growth of the CAR-T cells in the patient's body while at the same time suppressing growth of other T-cells, which if theory holds would enable much stronger therapeutic outcomes for patients with B-cell malignancies than in vivo CAR-T therapies only carrying a CAR transgene payload.

Related Pipeline Assets

UB-VV500: same underlying delivery mechanism as Umoja Bio's other therapies, but targeting BCMA and GPRC5D for multiple myeloma.^[14] UB-VV500 is set to enter phase 1 trials in H2 of 2026.^[15]

UB-VV300/310: Additional therapies in preclinical stages (targeting non-Hodgkin Lymphoma and Autoimmune disease) along with multiple other undisclosed assets in hematology and oncology.^[15]

2. UB-VV400 (Umoja Biopharma)

Name(s)	UB-VV400, UB-VV400/410 (i.e., 400 and 410 being closely related investigational therapies, with one likely focused on NHL and the other autoimmune indications)
Therapeutic Strategy	Permanent CAR expression
Delivery Vector	Modified lentivirus^[16]
Payload	Anti-CD22 CAR transgene; Rapamycin Activated Cytokine Receptor (selective growth switch for CAR-T cells in the body and suppression of other T cells)^[9]
Lead Indication	Clinical trial is centered on Relapsed/Refractory Large B-Cell Lymphomas, although sponsor pipeline page indicates the therapy is also designed for autoimmune indications^[17]^[15]
ROA	Intravenous (likely also Intranodal)
Sponsor(s)	Umoja Biopharma, Nanjing IASO Biotechnology (partnership with IASO where Umoja owns ex-China global rights and IASO owns in-China commercialization rights)^[18]
Sponsor Country	US, China
Trial Name / NCT ID	NCT06743503^[17]
Trial Phase	Phase 1 (China only)

Trial Progress, Data Readouts, Next Milestones

The most recent update on this China-based trial was a delay in expected data readout, with interim results now targeted for H2 of 2026.^[19]

Competitive Advantage / Bold Bet

Related Pipeline Assets

See other Umoja assets listed above.

3. KLN-1010 (Eli Lilly)

Name(s)	KLN-1010 (Eli Lilly will likely rename the asset soon as the acquisition was very recent)^[20]
Therapeutic Strategy	Permanent expression
Delivery Vector	Modified lentivirus
Payload	Anti-BCMA CAR transgene^[20]
Lead Indication	Relapsed/Refractory Multiple Myeloma
ROA	IV^[21]
Sponsor(s)	Eli Lilly (formerly Kelonia Therapeutics prior to acquisition)^[20]
Sponsor Country	US (both)
Trial Name / NCT ID	inMMyCAR (NCT07075185)^[22]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

The most recent interim results from the phase 1 study were released in June 2026 at ASCO. All 6 infused patients were minimal residual disease negative after one month, with the first dosed patient having maintained MRD negativity beyond 10 months.^[23] Two-thirds of patients with more than 4 months of follow-up have also demonstrated stringent complete response, and the other third very good partial response.^[24] Data will need to continue maturing as follow-up and participant dosing continues.

Competitive Advantage / Bold Bet

The company's in vivo gene placement system (engineered lentivirus) may have undisclosed proprietary advantages. Aside from that, the drug payload is a standard transgene without any other components. Although the delivery vector and payload may not be competitively differentiated, phase 1 results for the therapy show sweeping efficacy across all participants, suggesting a potential efficacy advantage.

Related Pipeline Assets

None at this time.

4. ESO-T01 (AstraZeneca)

Name(s)	ESO-T01
Therapeutic Strategy	Permanent expression
Delivery Vector	Modified lentivirus^[25]
Payload	Anti-BCMA CAR transgene^[25]
Lead Indication	Relapsed/Refractory Multiple Myeloma
ROA	IV^[25]
Sponsor(s)	AstraZeneca, EsoBiotec (was acquired, AstraZeneca fully owns the asset)^[26]
Sponsor Country	UK, Belgium
Trial Name / NCT ID	NCT06791681^[27], NCT06691685^[28]
Trial Phase	Phase 1 (both trials set in China only)

Trial Progress, Data Readouts, Next Milestones

NCT06791681 was stopped early in 2025 due to a trial death, attributed to a preexisting lesion on the patient's spine that made the CAR-T treatment and its associated side effects much riskier for the participant.^[26] Beyond the singular death event, all participants that received an infusion experienced grade 3+ AEs, with 3 participants experiencing grade 3+ Cytokine Release Syndrome (a very serious AE).^[25] Despite unfavorable safety outcomes, efficacy results still held promise, with objective response in 4 participants (3 of which were stringent complete remissions) and MRD negativity in all four evaluable respondents by day 60.^[25]

While NCT06791681 has been stopped, NCT06691685 appears to be ongoing.

Competitive Advantage / Bold Bet

ESO-T01 is currently disadvantaged due to the severe adverse effects and patient death associated with the therapy's phase 1 trial, representing an uphill climb to justify additional investments in phase 2 trials. Probable grade 3+ CRS and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) would mean drastically limited therapeutic and commercial viability.

Related Pipeline Assets

None at this time.

5. LB2501 (Legend Biotech)

Name(s)	LB2501
Therapeutic Strategy	Permanent expression
Delivery Vector	Modified lentivirus^[29]
Payload	Anti-CD19/CD20 dual-targeting CAR transgene^[30]
Lead Indication	Relapsed/Refractory B-Cell Non-Hodgkin Lymphomas
ROA	IV
Sponsor(s)	Legend Biotech
Sponsor Country	US/China Hybrid (company originated in China but has established global HQ in the US, with a lot of R&D still based in China)
Trial Name / NCT ID	NCT07002112^[31]
Trial Phase	Phase 1 (set in China only)

Trial Progress, Data Readouts, Next Milestones

Preliminary results from 12 dosed patients revealed no serious AEs across the dose level cohorts. No ICANS were observed, and CRS events were only grades 1-2.^[29] Dose level 2 cohort (N=6) had 100% objective response rate and a 83.3% complete response rate.^[30] Pharmacokinetic data showed that CAR-T cell persistence in peripheral blood was still positive after 116 days.^[32]

Competitive Advantage / Bold Bet

LB2501's main competitive advantage lies in its proprietary CD19/CD20 dual targeting CAR, where most first generation CAR-Ts and novel in vivo CAR-Ts in development are only going after a single antigen at a time. This dual targeting enables T-cells with another layer of cancer cell identification and killing. It may be a big factor in the extremely high and sustained response rates that the Phase 1 Dose Level 2 cohort trial interim results have demonstrated.

Related Pipeline Assets

While LB2501 is Legend's lead asset, the company lists two additional in vivo CAR-T therapies on their website, both also listed as enrolling for phase 1 trials^[33]:

LB2503 - anti-GPRC5D payload
LB2505 - anti-BCMA payload

However, neither of these phase 1 trials can be found registered on clinicaltrials.gov or the China trials registry, indicating these two therapies may be lagging behind LB2501.

6. INT2104 (Kite Pharma/Gilead)

Name(s)	INT2104
Therapeutic Strategy	Permanent expression
Delivery Vector	Modified lentivirus, targeting not only T-cells but also NK cells for transduction^[34]^[35]
Payload	Anti-CD20 CAR transgene
Lead Indication	Relapsed/Refractory B-cell Malignancies
ROA	IV
Sponsor(s)	Kite Pharma (parent company Gilead); asset originally developed by Interius Biotherapeutics^[36]
Sponsor Country	US (both)
Trial Name / NCT ID	INVISE (NCT06539338)^[37]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

Data has not yet read out from the trial, with the most recent data on the asset appearing to come from preclinical trial results.^[38]

Competitive Advantage / Bold Bet

INT2104 is unique in the in vivo CAR-T landscape in that the lentiviral delivery vector's guiding binder (CD7) not only targets T-cells but also Natural Killer (NK) cells, recruiting a larger array of cell types for cancer targeting. This has the potential for greater therapeutic effect than that of in vivo CAR-Ts without any NK cell transduction capabilities.

Related Pipeline Assets

None at this time.

7. CPTX2309 (AbbVie)

Name(s)	CPTX2309
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle (TLNP)
Payload	Anti-CD19 CAR mRNA^[39]
Lead Indication	Moderate to Severe Rheumatoid Arthritis (RA) or Systemic Lupus Erythematosus (SLE)^[40]
ROA	IV
Sponsor(s)	AbbVie (asset ownership through acquisition of Capstan Therapeutics)^[41]
Sponsor Country	US (both)
Trial Name / NCT ID	NCT06917742^[40]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

Phase 1 interim data has not yet read out.

Competitive Advantage / Bold Bet

Disclosed information does not present a unique competitive advantage of the TLNP delivery vector or the mRNA payload.

Related Pipeline Assets

None at this time.

8. HN2301 (MagicRNA)

Name(s)	HN2301
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle
Payload	Anti-CD19 CAR mRNA
Lead Indication	Autoimmune Diseases including Systemic Lupus Erythematosus, Systemic Sclerosis, Rheumatoid Arthritis^[42]
ROA	IV
Sponsor(s)	Shenzhen MagicRNA Biotechnology
Sponsor Country	China
Trial Name / NCT ID	NCT06801119^[42]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

Most recent results from the phase 1 trial include six patients that have received an infusion. Results focused on measuring molecular disease activity (i.e., depletion of B-cells), safety, and microbiological disease activity. For safety, no high grade (assumed grade 3+) CRS or ICANS was observed.^[43] Disease activity demonstrated effective B-cell depletion as well as reduced Systemic Lupus Erythematosus disease activity.

Competitive Advantage / Bold Bet

While MagicRNA's proprietary Engineered Cell-targeted LNP (EnC-LNP) technology may offer drug delivery / T-cell targeting potency advantages, there are no specific delivery vector or payload design components that confer a competitive advantage for HN2301.

Related Pipeline Assets

None at this time.

9. ORN-252 (Eli Lilly)

Name(s)	ORN-252
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle
Payload	Anti-CD19 CAR circular mRNA
Lead Indication	B-cell driven autoimmune diseases
ROA	IV
Sponsor(s)	Eli Lilly (through acquisition of Orna Therapeutics)^[44]
Sponsor Country	US (both)
Trial Name / NCT ID	NCT07439796^[45]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

The trial has only recently kicked off earlier this year, with no readout yet. Orna presented preclinical data in late 2025 on ORN-252. Promising data on B-cell killing and CAR-T expression was revealed, with roughly 2-3 weeks of persistent treatment effect observed.^[46]

Competitive Advantage / Bold Bet

Circular RNA technology presents an advantage as persistent drug effect is a limitation of mRNA based therapies. The circular design leads to longer RNA half-life and increased protein expression, ultimately leading to a drug that can have greater therapeutic effect and less frequent patient dosing.^[47]

Related Pipeline Assets

None at this time.

10. MT-302 (CREATE Medicines)

Name(s)	MT-302
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle (aimed at myeloid cells as opposed to T-cells)^[48]
Payload	Anti-TROP2 CAR mRNA^[49]
Lead Indication	Frontline gastroesophageal junction (GEJ) adenocarcinoma
ROA	Unclear (likely IV)
Sponsor(s)	CREATE Medicines (formerly branded as Myeloid Therapeutics)^[50]
Sponsor Country	US
Trial Name / NCT ID	MYE-Symphony (NCT05969041)^[51]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

Preliminary results from MYE-Symphony were published in November 2025. Results indicated an overall manageable safety profile, with no grade 3+ CRS and one grade 4 ICANS.^[52] Successful CAR+ myeloid cell penetration of solid tumors was also observed.

Competitive Advantage / Bold Bet

MT-302 is unique in that it's a transient CAR expression therapy chasing after oncology (as opposed to autoimmune diseases).

Targeting myeloid cells as opposed to T-cells is also a less common proposition. While this was CREATE Medicine's siloed approach early on, they have expanded to also target T-cells like other pipeline competitors. This makes sense given myeloid cell transduction alone may not be sufficient for cancer treatment, but in combination with T-cell transduction may lead to more effective therapeutic outcomes.^[53]

The linear mRNA strand has also been engineered for greater durability and expression.^[49]

Related Pipeline Assets

CREATE is traveling off the beaten path with their in vivo bet in oncology, which may pay off and help differentiate the therapy as a unique in vivo CAR treatment option for patients if and when it enters the oncology treatment landscape.

CREATE has additional in vivo CAR oncology pipeline assets, including:

MT-303: anti-GPC3 CAR mRNA payload, targeting myeloid cells; intended to treat hepatocellular carcinoma and currently in phase 1 of clinical trials^[54]^[55]
MT-304: anti-HER2 CAR mRNA payload, targeting both myeloid and natural killer cells; intended to treat HER2-expressing solid tumors and currently in phase 1 of clinical trials^[54]^[56]
CRT-401: anti-HER2 and anti-TROP2 dual CAR mRNA payload, targeting myeloid, natural killer, and T-cells. The therapy is aiming for a phase 1 clinical trial as its next milestone.^[49]

These assets present additional competitive advantages, such as programming of multiple immune cells at once (T, NK, myeloid) as opposed to T-cell targeting alone.

11. JCXH-213 (Immorna)

Name(s)	JCXH-213
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle
Payload	Anti-CD19 CAR mRNA^[57]
Lead Indication	B-cell Non-Hodgkin Lymphoma^[57]
ROA	IV (not confirmed but likely)
Sponsor(s)	Immorna
Sponsor Country	China
Trial Name / NCT ID	NCT06618313^[58]
Trial Phase	Phase 1

Trial Progress, Data Readouts, Next Milestones

While no data appears to have surfaced from the B-cell NHL trial, Immorna did recently announce data demonstrating thorough B-cell depletion in a Systemic Sclerosis patient.^[59]

Competitive Advantage / Bold Bet

Molecular design of JCXH-213 does not indicate any particularly unique competitive advantages.

Related Pipeline Assets

None at this time.

12. STR-P004 (Starna)

Name(s)	STR-P004
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle
Payload	Anti-CD19 CAR mRNA^[60]
Lead Indication	Autoimmune disease
ROA	IV
Sponsor(s)	Starna Therapeutics
Sponsor Country	China
Trial Name / NCT ID	NCT07143617^[61]
Trial Phase	NA (labeled as an 'exploratory clinical trial,' can be considered pre-phase 1)

Trial Progress, Data Readouts, Next Milestones

Set in China, this exploratory study evaluated safety and early efficacy outcomes of STR-P004 in relapsed/refractory autoimmune disease patients. Results were published in May 2026 from n=3 treated patients. No patients developed ICANS (CRS was not reported on). Intended B-cell depletion as well as improved disease activity were observed across the patients.^[60]

STR-P004 is also being evaluated in additional clinical trials targeting oncology:

Acute lymphoblastic leukemia (NCT07245251)^[62]
B-cell Non-Hodgkin Lymphoma (NCT07003178)^[63]

Competitive Advantage / Bold Bet

Starna emphasizes the tissue-specificity of their targeted lipid nanoparticles, which may prove to be an advantage for enhanced drug effect and lower required dosing for patients.^[64]

Related Pipeline Assets

Starna has an additional in vivo CAR-T pipeline asset STR-P005, which is currently only targeting autoimmune disease, with two exploratory clinical trials:

NCT07655453^[65]
NCT07605637^[66]

13. CRT-402 (CREATE Medicines)

Name(s)	CRT-402
Therapeutic Strategy	Transient expression
Delivery Vector	Targeted lipid nanoparticle
Payload	Anti-CD19 CAR mRNA
Lead Indication	B-cell driven autoimmune disease^[67]
ROA	IV
Sponsor(s)	CREATE Medicines
Sponsor Country	US
Trial Name / NCT ID	NA
Trial Phase	Preclinical

Trial Progress, Data Readouts, Next Milestones

While the phase 1 trial has not yet begun, CREATE anticipates it will enter the clinic soon, with preliminary data readout expected by Q4 2026.^[67]^[49]

Competitive Advantage / Bold Bet

While CREATE's line of oncology assets offer several unique competitive advantages, their bet in autoimmune with CRT-402 follows a more standard approach (i.e., targeting T-cells with a single CAR).

However, use of the same LNP and mRNA platform means the same advantages with their uniquely engineered linear mRNA also apply to CRT-402.

Related Pipeline Assets

See other CREATE assets listed above.

14. CRT-403 (CREATE Medicines)

Name(s)	CRT-403
Therapeutic Strategy	Permanent expression
Delivery Vector	Targeted lipid nanoparticle
Payload	Anti-CD19 and BCMA dual-CAR RNA
Lead Indication	Autoimmune (specific indication TBD)
ROA	IV
Sponsor(s)	CREATE Medicines
Sponsor Country	US
Trial Name / NCT ID	NA
Trial Phase	Preclinical

Trial Progress, Data Readouts, Next Milestones

CRT-403 is expected to enter phase 1 clinical trials sometime in 2027-2028.^[49]

Competitive Advantage / Bold Bet

CRT-403 represents one of the most novel and compelling approaches for in vivo CAR-T therapy. The RetroT platform is intended to use LNP delivery of RNA cargo for permanent expression of CAR-Ts. This would be a huge achievement and improvement in the field since lentiviral delivery vectors are much more difficult to manufacture than LNPs.^[68]

Related Pipeline Assets

See other CREATE assets listed above.

Additional Clinical-Stage Assets Worth Noting

KJ-C2529: a CD19/CD20 targeting in vivo CAR-T developed by Carsgen Therapeutics intended to treat B-cell malignancies.^[69] The asset appears to be entering an investigator-initiated phase 1 clinical trial in China expected to kick off in H2 2026.^[70] Trial ID is likely NCT07362602 but not definitive.^[71] Carsgen has multiple additional pre-clinical stage in vivo CAR-T assets listed in their pipeline, with molecular targets including BCMA, CD19, Claudin18.2, GPRC5D, and GPC3.^[69]
JY231: While not yet official in clinical trials, Genocury's CD19 targeting in vivo CAR-T has entered into multiple investigator-initiated trials in leukemia indications (NCT06678282 and NCT06514768).^[72]^[73]^[74]
LV009: PersonGen's leading in vivo CAR-T asset targets CD19 and is pursuing B-cell acute lymphoblastic leukemia, Non-Hodgkin Lymphoma, and autoimmune disease.^[75] PersonGen has recently kicked off its phase 1 trial in China (NCT07284927).^[76] While unclear if it specifically applies to LV009, the company's in vivo CAR platform targets not only T-cells but also natural killer cells, offering a competitive advantage.^[77]

Concluding Remarks

A key hallmark of the in vivo CAR-T landscape is that numerous drug developers have multiple assets in their pipeline all advancing to the clinic in tandem. This is because the innovation largely lies in the platform; after developing a proprietary delivery vector (either a modified lentivirus or targeted LNP) along with either a nondifferentiated or a more unique genetic payload (e.g., circular mRNA, supplemental rapamycin receptor, etc.), it is relatively simple to swap out the specific CAR being delivered (e.g., CD19, BCMA, etc.) as well as the surface protein of the vector for what immune cells it's targeting (e.g., T, myeloid, NK, etc.).

Two notable powerhouses leveraging this platform interchangeability are Umoja Biopharma and CREATE Medicines.

Umoja Biopharma is a powerhouse in the in vivo CAR-T space, with an entire pipeline of half a dozen candidates spanning preclinical to phase 1 trials. They are leveraging their unique rapamycin-controlled high-potency delivery and CAR-T cell proliferation platform VivoVec with various prominent molecular targets to push their pipeline into the clinic.

CREATE Medicines is another in vivo CAR-T juggernaut, boasting their own set of six pipeline assets. Many of their assets are already in the clinical stage or about to enter it. Furthermore, CREATE has multiple distinct competitive advantages, including its optimized linear mRNA technology, targeting of multiple immune cell types beyond T-cells, and its dual-CAR therapies, as well as its more novel RetroT platform to achieve permanent CAR-T expression with targeted LNP delivery as opposed to a lentiviral vector. CREATE truly does stand out as an innovative player in the space with multiple different bets in both oncology and autoimmune disease.

While this report aims to cover the most important technologies and where they are in development, the in vivo CAR-T development pipeline is extensive and there are many more assets in the global pipeline. For further reading, below are two wonderful deep dive publications / reports on the entire in vivo CAR-T landscape:

William Blair (Investment Bank), October 2025 Report^[78]
Pierini et al. In Vivo CAR-T Overview Paper in the International Journal of Molecular Sciences, February 2026^[79]

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References(click to expand)

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In Vivo CAR-T Landscape: T-cell Reprogramming Directly in Patients

History of CAR-T Therapy

Therapeutic Approaches & Targets

Pipeline Overview

Pipeline Deep Dive

1. UB-VV111 (Umoja Biopharma)

2. UB-VV400 (Umoja Biopharma)

3. KLN-1010 (Eli Lilly)

4. ESO-T01 (AstraZeneca)

5. LB2501 (Legend Biotech)

6. INT2104 (Kite Pharma/Gilead)

7. CPTX2309 (AbbVie)

8. HN2301 (MagicRNA)

9. ORN-252 (Eli Lilly)

10. MT-302 (CREATE Medicines)

11. JCXH-213 (Immorna)

12. STR-P004 (Starna)

13. CRT-402 (CREATE Medicines)

14. CRT-403 (CREATE Medicines)

Additional Clinical-Stage Assets Worth Noting

Concluding Remarks

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