Recently, various academic conferences in the global pharmaceutical industry, such as ASGCT, ASCO, EHA, have been held one after another. In vivo CAR-T, as one of the hottest tracks, has also begun to submit its first batch of papers after more than two years of saturated innovation.

 

From lentivirus to LNP, from single target to dual target, companies including Kelonia under Eli Lilly, as well as Legendary Biotech, Wistron Biotech, and Weitao Biotech, successively announced their clinical data on CAR-T therapy in vivo at the conference.

 

In the early stages, due to the lack of clinical data, investors mainly make forward-looking investments based on team background and technical concepts. At the earliest stage of the technical curve and the most ambiguous stage of cognition, they bet on potential directions with relatively low valuations. This strategy has obvious risk investment characteristics and tests the judgment of trends.

 

As more and more companies enter the IIT (Investigator Initiated Clinical Trials)/Phase I clinical stage, the balance of investment decisions begins to tilt towards data.

 

2026 is a crucial year for in-vivo CAR-T therapy, and with the milestone of multiple companies disclosing clinical data, the in-vivo CAR-T track will also enter a period of centralized validation. Of course, for some players, this process may also be a round of falsification test.

1、slow virus route centralized verification

Why should Kelonia be acquired again after the in vivo CAR-T company has already acquired the circular RNA route? And at a high price of 7 billion US dollars? This is one of the biggest doubts for the pharmaceutical industry in the first half of this year.

Prior to the acquisition by Eli Lilly, Kelonia released the first human data of KLN-1010 treatment for recurrent/refractory multiple myeloma (r/r MM) patients at the 2025 ASH Annual Meeting in December of last year, with only four patients at the time. The latest data, released at the end of May at the 2026 ASCO Annual Meeting, has been expanded to 18 cases, making it the world's largest in vivo CAR-T clinical dataset to date.

On the efficacy level, all 18 patients achieved minimal residual disease (MRD) negative bone marrow and an ORR of 100% one month after treatment. The first patient to receive treatment is still in deep and sustained MRD negative remission for over 10 months. Among the 6 patients followed up for ≥ 4 months, 4 achieved strict complete remission, 2 achieved very good partial remission, and all patients' bone marrow remained MRD negative.

In terms of safety, 16 out of 18 patients developed grade 1-2 CRS, with no severe CRS, only 1 case of grade 1 and 1 case of grade 3 ICANS (lasting for 3 days), and no delayed neurotoxicity was observed. The safety review committee has approved KLN-1010 for outpatient infusion administration.

Kelonia founder and CEO Kevin Friedman believes that this safety feature makes KLN-1010 "highly likely" to be pushed towards earlier line treatments.

KLN-1010 is an in vivo CAR-T cell therapy targeting BCMA, based on Kelonia's proprietary iGPS ® (In vivo gene localization system) platform development. Unlike traditional lentiviral vectors, iGPS ® The core innovation of the platform lies in its "active targeting" mechanism, which modifies the lentiviral vector by adding targeting molecules and fusion promoting molecules to achieve tissue-specific delivery.

Jacob Van Naarden, Head of Oncology and Business Development at Eli Lilly, described this data as "nutty" (shocking), stating that achieving 100% response rate and MRD negativity in the most heavily pretreated patients is unprecedented.

Although Kelonia initially tested 4 patients in Australia, the trial has now expanded to the United States and is ongoing to determine the optimal dosage for subsequent development. Although the acquisition is not yet completed, Van Naarden has met with multiple myeloma experts during ASCO to explore the best path for KLN-1010 to enter phase III trials.
After Kelonia, legendary creatures added another flame to the slow virus route.

In early June, Legendary Biotech released its first human data on its CAR-T therapy LB2501 in relapsed/refractory non Hodgkin's lymphoma, causing the company's stock price to soar 42% on the same day.

LB2501 is the first CD19/CD20 dual targeted in vivo CAR-T based on TaVec ™ Platform development, this platform is a proprietary lentiviral vector designed to enhance T cell targeting specificity, transduction efficiency, and safety, while limiting transduction to non T cells.

As of April 1, 2026, 12 patients with relapsed/refractory B-cell non Hodgkin's lymphoma (R/R B-NHL) who had previously received ≥ second-line treatment received treatment. Among the 6 patients in the dose level 2 (DL2) cohort, the ORR reached 100%, the complete response rate was 83.3% (5/6), and the median follow-up was 2.2 months, with all responses still ongoing.
Pharmacokinetic analysis confirmed dose-dependent expansion of CAR-T cells in vivo, with CAR-T cells detectable in peripheral blood for up to 116 days in the DL2 cohort.
In terms of safety, no dose limiting toxicity, serious adverse events, or deaths were observed. 75% of patients experienced infusion related reactions and 66.7% experienced CRS, but both were grade 2 or below; No immune effector cell related ICANS reported.

In addition, EsoBiotec (acquired by AstraZeneca) updated ESO-T01 data in Nature Medicine in March this year -4 out of 5 patients achieved objective remission (3 sCR, 1 PR). In terms of safety, 4 patients developed CRS (3 grade 3, 1 grade 2), 1 patient developed grade 1 ICANS, and died on the 19th day after treatment due to spinal cord compression caused by extramedullary lesions.

Overall, the clinical prospects of in vivo CAR-T using the lentiviral route in hematological tumors have been preliminarily validated.
The above data collectively demonstrate that macromolecular lentiviral vectors can efficiently and selectively transduce T cells in the human body, producing CAR-T cells with strong anti-tumor activity without the need for lymphocyte clearance pretreatment, and achieving deep and lasting remission in some patients.

However, the sample size of the existing data is still relatively small (the largest KLN-1010 only has 18 cases), and there is a lack of randomized controlled design. The inMMyCAR study of KLN-1010 aims to enroll 40 cases, and its clinical value can only be more accurately evaluated after completing all enrollments and obtaining a median follow-up of at least 12 months.

 

2、Different logics of LNP routes

If the slow virus route inherits the traditional CAR-T technology logic of "one-time infusion, long-term persistence", then the LNP mRNA route has taken a completely different path.
By delivering mRNA encoding CAR to T cells through LNP, CAR is transiently expressed in vivo and naturally degraded upon completion of its mission - it does not integrate with the genome and does not involve the risk of off target gene insertion. The disadvantage is that the transient expression of mRNA means that CAR-T cells have limited persistence and may require multiple administrations to maintain efficacy.

At the 2026 ASCO Annual Meeting, the LNP route also presented its answer sheet.

Wiszin Biotech has released the first human data of WGb-0301 in Rapid Oral format. WGb-0301 is based on the CD8 targeted LNP platform and generates anti-CD19 CAR-T in situ in patients through mRNA technology, without the need for complex in vitro preparation procedures and clear lymph pre-treatment, significantly shortening the treatment cycle.

After treatment, 4 patients with relapsed/refractory B-cell lymphoma were able to rapidly induce CAR expression within 4-6 hours after administration, with a CAR positivity rate of up to 100%, and successfully achieved up to 10 repeated administrations.

In terms of efficacy, one patient with mantle cell lymphoma (MCL) achieved complete remission (CR) after 10 doses, one patient with diffuse large B-cell lymphoma (DLBCL) achieved partial remission (PR), and there were also one MCL and one DLBCL patient with disease stability (SD) and disease progression (PD), respectively. In terms of safety, all treatment-related adverse events were grade 1-2, and no grade ≥ 3 events occurred.

The first human study data of GT801 in recurrent/refractory B-cell hematological tumors was also reported in the form of a poster on ASCO, using Micro Tao Biotechnology derived from Sandstone Bio.

GT801 uses lipid nanoparticle (LNP) delivery technology targeting T cells to complete T cell transfection in patients. Without the need for in vitro cell preparation or lymphatic clearance pretreatment, CAR-T cells expressing CD19 CAR can be generated in vivo.

As of May 15, 2026, a total of 4 patients with relapsed/refractory B-cell non Hodgkin's lymphoma (B-NHL) have received GT801 treatment, including 1 case of marginal zone lymphoma (MZL), 1 case of diffuse large B-cell lymphoma (DLBCL), and 2 cases of follicular lymphoma (FL). The patient received median 2.5-line treatment in the past.

In terms of efficacy, the objective response rate (ORR) of 4 patients reached 100%, with 3 patients ultimately achieving complete response (CR). All patients achieved partial response (PR) during the initial efficacy evaluation, and the efficacy continued to deepen thereafter, maintaining CR status as of the data deadline.

GT801 exhibits rapid and efficient in vivo CAR-T generation ability - CAR-T cells can be detected in peripheral blood 4 hours after administration and reach transfection peak on Day 1. The peak proportion of peripheral blood CAR+T cells exceeds 90% and continues to maintain high levels of expression after repeated administration. Meanwhile, CAR expression in monocytes was observed to be below 3%, demonstrating excellent targeting specificity.

In terms of safety, no infusion related reactions were observed with GT801, and CRS was effectively controlled at grade 0-1 under pre-treatment medication conditions. All grade 3 and above adverse events were reversible hematological toxicity, and no dose limiting toxicity (DLT), neurotoxicity, or organ failure events were observed.

Beyond the field of oncology, Hongxin Biotechnology has also taken the lead in expanding LNP mRNA in vivo CAR-T to autoimmune diseases.

In September 2025, its product HN2301 completed the world's first human report in the treatment of refractory systemic lupus erythematosus (SLE), achieving deep clearance of B cells in 5 patients without the need for lymphocyte clearing pretreatment, with good safety. The results were published in the New England Journal of Medicine (NEJM). Recently, this study has been selected for the ASGCT Annual Conference Oral Presentation and EULAR Conference Highlights, and its international academic recognition continues to rise.

From existing clinical data, the performance of the two major technological routes basically conforms to their mechanism characteristics: representative products of the lentiviral route demonstrate strong CAR-T amplification and persistence, while representative products of the mRNA LNP route demonstrate excellent safety.

However, the transient expression of mRNA LNP also brings persistent uncertainty - is it sufficient to achieve persistent immune reset in autoimmune diseases? Does the field of oncology require more frequent drug administration to maintain therapeutic efficacy? These require longer follow-up and larger sample sizes of data to answer.

 

3、BD opportunities for domestic pipelines

The craze for CAR-T in vivo has also begun to enter the moment of clinical data speaking. In a sense, 2026 is the critical window for in vivo CAR-T validation.

According to the Dingxiangyuan Insight database, in 2023, there were only 2 in vivo CAR-T pipelines under development that entered the clinical application stage or above globally. However, as of April 2026, this number has increased to 43, a surge of 2050%. Such dense pipeline advancement means that a large amount of clinical data will be read out in the coming years.

In addition to the aforementioned companies, overseas pharmaceutical companies such as Gilead, AbbVie, AstraZeneca, BMS, and Umoja, as well as domestic players such as Yunding Xinyao and Jiachen Xihai, have clinical layouts in the field of in-vivo CAR-T and are actively promoting it. The clinical results of these players will be gradually announced.
Dongfang Securities believes that all four overseas in-vivo CAR-T companies in the top tier of global clinical progress, except for Umoja, have been acquired by MNC, highlighting the scarcity of targets. At present, the majority of clinical pipelines are domestically produced, and it is expected that multiple models will disclose clinical data for the first time this year. If the data is positive, the platform is validated, and has differentiation advantages, domestic pipelines are expected to usher in BD opportunities.

In fact, domestic pipelines have begun to receive substantial recognition from MNC. Last October, Kite, a subsidiary of Gilead, reached an in vivo CAR-T authorization cooperation with Prudential Biologics. Prudential received a down payment of $120 million and a milestone payment of up to $1.52 billion, becoming the first BD transaction for in vivo CAR-T therapy in China.

More commercially significant is that on June 9th, following the release of WGb-0301 data from Wistron Biologics, Cartesian Therapeutics announced a strategic partnership with Wistron Biologics. Affected by this news, Cartesian's stock price rose by over 16% at one point.

Both parties plan to combine the Wisconsin Biotargeted LNP delivery platform with Cartesian Descartes-08 mRNA payload (mRNA CAR-T) to jointly develop in vivo CAR-T therapy for autoimmune diseases. The first collaborative project focuses on systemic myasthenia gravis (gMG), with plans to launch Phase I clinical trials in the second half of 2026 and release the first batch of human data in the first half of 2027.

2026 is becoming a watershed for the CAR-T circuit in the body to move from "proof of concept" to "value realization". As more clinical data is gradually read out, the value of the technology platform will be tested by the real world; And MNC's "sweeping" of overseas targets is coming to an end, and the scarcity dividend is accelerating to overflow into domestic pipelines.

The collaboration between Wesson and Cartesian, as well as the authorization transaction between Prikin and Gilead, are just the beginning of this trend. Next, domestic players with solid data and differentiated advantages are expected to occupy a more proactive position at the BD negotiation table. The story of CAR-T in the body seems to have just opened the most exciting chapter.

 

Reference materials:

1 Kelonia Therapeutics Presents Updated First-in-Human Data from Phase 1 inMMyCAR Study of KLN-1010 in vivo BCMA CAR-T Therapy at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting 
2.FierceBiotech，ASCO: Lilly exec points to ‘nutty’ 100% response rate for in vivo CAR-T as justifying Kelonia buyout
3.FierceBiotech，AstraZeneca’s in vivo CAR-T bet eradicates cancer in 3 of 5 patients, but death mars dataset
4. Official websites and WeChat accounts of various enterprises
Narrow Gate Medicine, In Vivo CAR-T Global Clinical Data Deep Analysis Report: Efficacy, Safety, Introversion, Endgame
6. Amino observation, CAR-T in the body has two brushes
7. Same expression, explosive ASGCT 2026: China's CAR-T multi platform racing in vivo