By Ignacio Urdaneta, Consultant and Kian Talaei, Engagement Manager

CAR‑T therapies have demonstrated what is possible when immune cells are precisely engineered to attack cancer. But after more than a decade of ex vivo development, the industry is encountering an evolving constraint: widespread operational feasibility. Autologous CAR‑T works, yet manufacturing timelines and complex treatment journey have historically challenged its ability to scale across diverse care settings and patient populations.

In vivo CAR‑T is emerging as the next frontier because it challenges the assumptions that define today’s CAR‑T model. Rather than manufacturing a cellular product outside the body, in vivo approaches deliver genetic instructions directly to immune cells within the patient. This shift has the potential to address core operational bottlenecks that limit current CAR‑T models: long vein‑to‑vein times, manufacturing slot availability & turnaround, and dependence on sophisticated health systems’ capacity, including apheresis infrastructure needs.

Why Health Systems, Manufacturers, and Commercial Teams Are Paying Attention

Traditional CAR‑T is built around a complex patient journey and manufacturing sequence, including apheresis, centralized processing, cell engineering and expansion, quality release testing, lymphodepletion, and product infusion. Each step introduces potential delays and coordination challenges, creating unique operational complexities across a broader range of sites that may participate in CAR‑T patient care.

In vivo CAR‑T reframes this model. By eliminating the need for ex vivo manipulation, these approaches could drastically reduce lead times and the burdens placed on specialized centers, enabling a more scalable model that resembles high‑complexity product administration rather than custom biologic manufacturing. 

The disruptive potential of in vivo CAR‑T is not simply that it represents the next scientific platform, it is that the new delivery model has the potential to expand access, as:

  • Time‑to‑treatment shortens. If in vivo approaches can eliminate apheresis and centralized manufacturing queues, the path from patient identification to infusion could shorten by 3 to 5 weeks. For aggressive diseases, reducing time to infusion improves access by allowing patients to be treated earlier, before progression or competing treatment needs emerge.
  • Site‑of‑care flexibility increases. While today’s CAR‑T ecosystem is concentrated in high‑capability health systems (e.g., academic), in vivo delivery raises the possibility of expanding access beyond these hubs (e.g., lack of need for apheresis, etc.).
  • Capacity scales differently. In vivo CAR-T does not rely on patient-specific manufacturing slots, enabling scalability that is not constrained by individualized production capacity. It also reduces the site-level infrastructure burden that limits today’s CAR-T programs such as apheresis needs. The result is a meaningful shift toward broader access: not quite the off-the-shelf simplicity of a traditional biologic, but substantially closer to it than current CAR-T delivery models. This changes how capacity planning, inventory management, and demand forecasting are approached, even if the full operational model of conventional biologics remains a longer-term horizon.

Operational improvements from in vivo CAR-T are a step in the right direction, but they will not drive greater adoption alone. In vivo CAR-T must still meet or exceed clinical benchmarks for depth of response, durability, and safety, and the broader ecosystem will need to evolve in parallel. Payer management models that make each patient a case rate negotiation, combined with nascent side effect and prophylactic treatment protocols, remain meaningful barriers regardless of how streamlined delivery becomes. If clinical outcomes fall short, or if access and reimbursement infrastructure fail to keep pace, operational improvements alone will not compensate.

Clinicians, payers, and providers will ask hard questions: Can responses match best‑in‑class autologous CAR‑T in comparable populations? Is toxicity predictable and manageable without shifting risk downstream to hospitals? Can exposure be controlled if adverse events emerge?

In Vivo May Bring CAR‑T Closer to Community Oncology

Today, there is structural misalignment between where a large proportion of patients are managed and where they can receive advanced care; a large proportion of U.S. oncology care occurs in the community setting, yet CAR-T treatment remains concentrated in sophisticated health systems. There has been a significant focus on the need to shift CAR‑T access closer to communities by expanding site capabilities and addressing operational barriers. In vivo CAR‑T can accelerate this shift by addressing key challenges that ex vivo community adoption currently faces.

By removing the need for apheresis, lymphodepletion, and cell processing infrastructure, the therapy begins to resemble complex infusion‑based oncology care rather than a bespoke transplant‑adjacent procedure. This opens the door for:

  • More community sites to participate in the administration pathway
  • Fewer referrals to sophisticated health systems for otherwise eligible patients
  • Reduced geographic inequities, particularly for rural or underserved regions
  • Improved care continuity, as patients can remain with their existing oncology teams

While in vivo CAR‑T may simplify parts of the delivery chain, it does not fully eliminate complexity. Community practices will still need:

  • Clear clinical protocols, including toxicity management
  • Partnership models with inpatient hospitals for escalation of care
  • Training and readiness programs, especially for CRS/ICANS management
  • Support navigating payer requirements, which remains a major barrier in cell therapy adoption
  • Workflow redesign, particularly around monitoring, scheduling, and coordination

The community practice opportunity is real but not automatic. Broad decentralization of CAR-T care will require more than the elimination of the manufacturing constraints, including addressing AE management complexity (e.g., high-grade CRS); otherwise, in vivo CAR-T risks a bispecific-like adoption ceiling rather than true democratization of care.

Why This Matters Now

The future of CAR-T will not be determined solely by platform science but by the ability of the broader oncology ecosystem to operationalize new care models. Manufacturers will need to drive change in how therapies are designed for real-world delivery. Payers will need to move beyond treating CAR-T as categorically different from other high-cost therapies, particularly as cost profiles converge, and reduce the administrative burden of single case negotiations. Providers will need to elevate their operational capabilities to meet the demands of an evolving therapy landscape.

For manufacturers already active in CAR-T, the key question is not whether in vivo approaches will replace ex vivo tomorrow, but how they challenge existing assumptions about operations, access, and scale. For those preparing for community-based expansion, it is how to redesign eligibility pathways and anticipate new workflow demands to be better positioned for a new CAR-T operating model.

 

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