News Watch: in vivo CAR-T RACE (2025 Global Update)

Last updated: 2025-09-01 JST

Lead: The shift from ex vivo to in vivo CAR-T is turning into a full-blown race. Big-ticket M&A, first-patient-dosed milestones, and multiple Phase-1 entries are consolidating the field into two lanes: lentiviral-like vectors (Umoja/Interius/Kelonia) and tLNP/mRNA (Capstan and peers). Clinical adoption will hinge on demonstrating lymphodepletion-sparing, re-dosing flexibility, target expansion, and real-world operational ease.

Three-Line Summary

• Capital consolidation: Kite (Gilead) to acquire Interius; AbbVie completed the Capstan deal—bringing in vivo platforms under big-pharma scale.
• Clinical momentum: Kelonia dosed the first patient in multiple myeloma; Interius and Umoja continue Phase-1 advances in hematologic cancers.
• Two modalities: Lentiviral-like vectors vs tLNP/mRNA. The deciding factors: lymphodepletion-sparing, re-dosing, and site-of-care logistics.

Why in vivo (now)?

Ex vivo CAR-T entails complex multi-step manufacturing and logistics, limiting access even among eligible patients. In vivo reframes the body as the CAR-T “factory,” bypassing bottlenecks in production and cold-chain. If dosing can be simplified, outpatient pathways and geographically distributed care models become attainable.

Company Highlights (Q3 2025)

Kite (Gilead) × Interius: $350M acquisition embeds in vivo

On Aug 21, 2025, Kite announced the $350M acquisition of Interius. Lead program INT2104 (CD20) began first-in-human in Australia and subsequently received EU expansion approval. Interius reported first-patient-dosed in Oct 2024 and has guided to initial readouts thereafter. Integration into Kite’s hematology franchise strengthens manufacturing and commercial readiness.

AbbVie × Capstan: tLNP/mRNA first in autoimmunity, oncology to follow

Following June announcement, the acquisition closed on Aug 19, 2025. Lead asset CPTX2309 (CD19, tLNP+mRNA) aims to transiently engineer T cells in vivo, with theoretical advantages in re-dosing and lymphodepletion sparing. Strategy: prove the concept in B-cell-mediated autoimmune disease, then expand to oncology.

Kelonia Therapeutics: anti-BCMA (KLN-1010) first-patient-dosed

On Aug 19, 2025, Kelonia dosed the first patient in the inMMyCAR Phase-1 trial in Australia. The program aspires to single-dose, lymphodepletion-free treatment in multiple myeloma. Near-term watch-items: outpatient feasibility, safety (fever/CRS), and delivery robustness.

Umoja Biopharma (+ AbbVie option): RACR × VivoVec for selective expansion

UB-VV111 (CD19, US) cleared IND in 2024 and is enrolling INVICTA-1. UB-VV400 (CD22, China IIT) also initiated. With the rapamycin-activated cytokine receptor (RACR), dosing rapamycin selectively expands CAR-modified cells while restraining bystanders—an elegant route to spare or simplify lymphodepletion.

Two Paths, One Goal

1) Lentiviral-like vectors (Umoja/Interius/Kelonia)

Optimized particles integrate genetic payloads into T cells to generate CAR-T in situ. Umoja’s VivoVec layers activation, co-stimulation, and genome integration. Interius targets CD20 for post-CD19 relapses, while Kelonia brings anti-BCMA with a lymphodepletion-sparing thesis.

2) tLNP/mRNA (Capstan and peers)

Targeted LNPs deliver CAR mRNA to T cells for transient CAR expression. The promise: re-dosing flexibility, shorter manufacturing lead-times, and outpatient-friendly workflows—prove it first in autoimmunity, then port to cancer.

Clinical KPIs to Watch

• Safety: fever/CRS, insertional risks, off-target effects, and iatrogenic immunosuppression. A “boring” safety profile in early cohorts is the biggest value driver.
• Lymphodepletion sparing: RACR + rapamycin should suppress non-CAR cells while expanding on-target CAR-T.
• Operational ease: single-visit dosing, outpatient viability, length of stay, and total episode cost across drug + premed + care.
• Target strategy: CD19/20/22/BCMA portfolio to capture post-CAR relapses; double-target logic for tougher segments.

Landscape (Q3 2025)

• Interius (Kite/Gilead): INT2104 (CD20)—Australia FIH → EU expansion; first-patient-dosed in 2024; acquisition boosts scale-up.
• Umoja (AbbVie option): UB-VV111 (CD19/US), UB-VV400 (CD22/China); RACR × VivoVec aims to simplify preconditioning and enable selective expansion.
• Kelonia: KLN-1010 (BCMA/Australia); testing a single-dose, lymphodepletion-sparing model for myeloma.
• Capstan (AbbVie): CPTX2309 (CD19/tLNP/mRNA/autoimmunity); integration under AbbVie tightens regulatory, CMC, and commercial pathways.

Outlook (My Take)

• Next 12 months: A quiet safety profile and operational wins (outpatient pathways, LOS reduction) will set the tone. Kelonia’s real-world logistics and Umoja’s RACR control are key catalysts.
• 1–3 years: If tLNP programs prove deep B-cell depletion with flexible re-dosing in autoimmunity, oncology expansion should follow. In heme-onc, CD22/BCMA and dual-target designs can differentiate in relapse populations.
• 3–5 years: Solid tumors will require a triad—multi-antigen logic, TME modulation, and regional delivery. Winners will stitch cross-platform coalitions (vectors × synbio × delivery) and build true site-of-care models.

Key References

• Kite (Gilead) to acquire Interius (Aug 21, 2025)
• AbbVie completed the Capstan acquisition (Aug 19, 2025)
• Kelonia dosed first patient with KLN-1010 (Aug 19, 2025)
• Umoja: UB-VV111 IND clearance (Jul 31, 2024), JPM-2025 deck
• Interius: INT2104 first-patient-dosed (Oct 23, 2024), EU expansion (Jan 7, 2025)

This article was edited by the Morningglorysciences Team.