In Vivo CAR-T Therapy Gains Momentum with Four New Clinical Programs Entering Phase 1 Studies
核心洞察
Four new in vivo CAR-T therapy programs have entered first-in-human studies, bringing the total number of clinical-stage assets in this emerging field to 16 programs.
Create Medicines (搜索)' MT-304 (搜索) targets HER2 (搜索)-positive solid tumors (搜索) using CAR-NK and CAR-myeloid cells, while Shenzhen Genocury (搜索)'s JY232 (搜索) focuses on BCMA (搜索)-positive multiple myeloma (搜索).
The rapid clinical expansion follows significant big pharma investments, including Bristol Myers Squibb (搜索)'s acquisition of Orbital Therapeutics and Gilead's takeover of Interius.
The in vivo CAR-T therapy field continues its rapid clinical expansion with four new programs entering first-in-human studies, demonstrating sustained industry confidence in this emerging approach that generates CAR-positive cells directly inside patients' bodies rather than through traditional ex vivo manufacturing.
Recent clinicaltrials.gov listings reveal that Create Medicines (搜索)' MT-304 (搜索) and Shenzhen Genocury (搜索)'s JY232 (搜索) have joined the clinical pipeline this month, following PersonGen (搜索)'s LV009 (搜索) and Legend's LVIVO-TaVec200, which recently entered phase 1 studies. These additions bring the total number of in vivo CAR-T assets in clinical development to 16 programs, up from 13 just months ago.
Novel Targeting Strategies Enter Clinical Testing
Create Medicines (搜索)' MT-304 (搜索) represents a significant departure from traditional CAR-T approaches by targeting HER2 (搜索)-positive solid tumors (搜索) using both CAR-NK and CAR-myeloid cells. The phase 1 trial will recruit patients with HER2-positive solid tumors, with some patients potentially receiving combination treatment with Opdivo.
This marks a strategic evolution for Create Medicines (搜索), formerly known as Myeloid Therapeutics, which rebranded in October 2023 to expand beyond its original focus on in vivo CAR-macrophages into T and NK cell therapies. MT-304 (搜索) appears to be the company's first clinical project utilizing cell types other than macrophages, following the phase 1 entries of myeloid cell CARs MT-303 (targeting GPC3 (搜索)) and MT-302 (targeting TROP2 (搜索)).
Meanwhile, Shenzhen Genocury (搜索)'s JY232 (搜索) takes a more conventional approach as a BCMA (搜索)-targeting in vivo CAR-T therapy for BCMA-positive multiple myeloma (搜索), though delivered through the innovative in vivo platform rather than traditional ex vivo manufacturing.
Expanding Clinical Pipeline Reflects Industry Momentum
PersonGen (搜索)'s LV009 (搜索), an anti-CD19 (搜索) lentivirus-based in vivo CAR-T therapy, has entered clinical testing for CD19-positive blood cancers (搜索). This represents the Chinese cell therapy company's first venture into in vivo CAR-T after extensive work on ex vivo anti-CD19 projects.
The rapid clinical progression has attracted substantial big pharma investment, with major acquisitions including Bristol Myers Squibb (搜索)'s purchase of Orbital Therapeutics, Gilead's takeover of Interius, AbbVie (搜索)'s acquisition of Capstan, and AstraZeneca's move on EsoBiotec.
Limited Clinical Data Despite Growing Pipeline
Despite the expanding pipeline, human efficacy data remain limited to case reports from two programs. Kelonia's KLN-1010 and EsoBiotec's ESO-T01, both BCMA (搜索)-targeting in vivo CAR-Ts, have each been tested in four patients, representing the only published human experience with this approach to date.
The field's first clinical entrant, Interius's INT2104, was cleared for human study just 18 months ago, making the current expansion to 16 clinical programs a remarkable achievement for such a nascent therapeutic approach.
Competitive Landscape Intensifies
The in vivo CAR-T field now encompasses diverse targeting strategies across hematologic malignancies and solid tumors (搜索). Beyond the newly entered programs, the clinical pipeline includes various approaches targeting antigens such as BCMA (搜索), CD19 (搜索), GPC3 (搜索), TROP2 (搜索), and GPRC5D (搜索) across multiple cancer types.
The technology aims to overcome traditional CAR-T manufacturing challenges by delivering genetic material directly to patients, potentially reducing costs and manufacturing timelines while expanding patient access to CAR-T therapies.