Will In Vivo CAR T Therapy Transform Cancer Treatment?

CAR T-cell therapies have transformed the treatment landscape for certain blood cancers, offering curative potential where conventional therapies fall short. Yet their impact has been constrained by high costs, complex manufacturing, and the need for specialist clinical infrastructure.

In vivo CAR T therapy—where a patient’s immune cells are engineered directly inside the body—aims to overcome these barriers, ushering in a more scalable and accessible model of cellular immunotherapy. 

Cancer Research Horizons’ On the Horizon event recently brought together world-leading experts on in vivo CAR T therapy to discuss whether this therapy will deliver on its game-changing potential. 

“Our On the Horizon events exist to connect the people and ideas shaping the future of cancer research, catalyzing the collaboration needed to beat cancer,”said Tony Hickson, chief business officer of Cancer Research Horizons. “We were delighted to bring together leading researchers, biotech founders, and investors to discuss the promise of in vivo CAR T therapies, and look forward to continuing these conversations, building new partnerships, and accelerating the translation of cutting-edge science to benefit people affected by cancer.” 

At the event, Technology Networks spoke with Dr. Saar Gill, founder of Interius Therapeutics and professor at the University of Pennsylvania, Dr. Rémi Soula, CEO of Thesian Bio, and Dr. Jonathan Tobin, investor-in-residence at Cancer Research Horizons and partner at Brandon Capital, to hear their perspectives on the potential and challenges of this emerging modality.  

Transforming access: Why in vivo CAR T therapy is generating momentum 

What is it about in vivo CAR T therapy that makes this modality so exciting? 

In vivo CAR T therapy is generating excitement largely because it has the potential to fundamentally alter how these powerful treatments are delivered and improve patient access.  

“There is potential for this technology to perform even better than ex vivo CAR T therapy.” — Dr. Rémi Soula 

Unlike ex vivo approaches—which require extracting, modifying, and reinfusing patient cells—this modality could enable CAR T therapies to be administered more like conventional medicines. As Tobin explained, the shift lies in converting a “clunky-to-administer” and resource-intensive therapy into something far more scalable and widely deployable. 

“It’s the ability to turn a product that has curative potential for patients, but is extremely expensive and clunky to administer, into something that's much more like a drug, and can be given to anyone, anywhere.” — Dr. Jonathan Tobin 

This transformation is particularly significant when viewed in the context of current access limitations.  

“There's a very limited percentage of patients who can access ex vivo CAR T treatment, despite the high eligibility,” Soula highlighted. This stark disparity between eligibility and actual treatment rates is driven largely by cost, which is typically around $400,000 per treatment. 

In vivo approaches promise off-the-shelf availability and lower production costs, potentially opening treatment to far broader patient populations. Crucially, these therapies may also eliminate the need for lymphodepletion, a preconditioning step that some patients cannot tolerate. 

Gill emphasized that accessibility gains may extend beyond high-income healthcare systems. If proven effective, in vivo CAR T therapies could improve access globally, including in resource-limited settings where current CAR T therapy infrastructure is infeasible.

“It’s going to vastly increase accessibility, both in affluent countries, but to me, even more excitingly, potentially in resource-poor settings as well.” — Dr. Saar Gill 

Early clinical signals suggest the approach is viable, reinforcing optimism across both academia and industry. 

Advantages of in vivo CAR T therapy: 

• Reduced cost compared with ex vivo CAR T therapies. 

• Potential for off-the-shelf, drug-like administration. 

• Elimination of lymphodepletion for patients. 

• Expanded global access, including low-resource settings. 

Technical and clinical barriers facing in vivo CAR T development 

What are the major hurdles to delivering in vivo CAR T therapy to patients? 

Despite its promise, in vivo CAR T therapy is in the early stages of clinical evaluation, and several uncertainties persist. Tobin noted that current evidence is derived from a limited number of patients, making it difficult to predict how broadly efficacy and tolerability will translate. While industry enthusiasm is high, there remains a real risk that results observed in early trials may not hold in larger, late-stage studies. 

“Based on the tiny amount of evidence we have, people have extrapolated to think that it will work everywhere, and I think there is a decent chance that it will, which is why pharma companies have piled in; they've assumed that it's going to work,” said Tobin. “I think there's also a risk that it doesn't pan out when it's tested in phase 3 trials in thousands of patients, and there's a risk that it doesn't work beyond the kind of small number of settings that have already been validated with autologous T cell therapies.”  

From a technical standpoint, one of the most significant challenges is cell specificity. Soula likened the process to navigating a maze: therapeutic vectors must reach and modify the correct immune cells without affecting unintended targets. Poor specificity could limit efficacy or introduce safety concerns. “There might be side effects associated with a lack of cell specificity,” he said. 

At the same time, sufficient transduction and expansion of CAR T cells are required to generate a therapeutic response. Encouragingly, early clinical data suggest that effective outcomes may be achievable across a range of transduction efficiencies. 

Safety remains a central concern. Overactivation of the immune system could lead to adverse effects, including cytokine release syndrome. Gill cautions that, at least in the near term, in vivo CAR T therapies are unlikely to become simple outpatient treatments, as patients will still require close monitoring and careful dose optimization. 

 “We don’t know yet whether there is a dose that is effective and completely without toxicity.” — Dr. Saar Gill 

Gill suggested that identifying the correct dosage for in vivo CAR T therapies—and understanding whether that dosage is the same for all patients—may form the next frontier for the therapy, especially in settings where its efficacy has been illustrated. 

Key development hurdles to address: 

• Limited clinical data and uncertainty in large-scale efficacy. 

• Challenges in achieving precise cell targeting. 

• Need for sufficient CAR T-cell expansion in vivo. 

• Managing safety risks, including cytokine release syndrome. 

Determinants of success in a crowded in vivo CAR T landscape 

What do you think will separate the successful in vivo CAR T therapies from the ones that fail during development? 

As more than 100 companies pursue in vivo CAR T strategies, differentiation will be critical. Tobin pointed to durability as a key determinant: longer persistence of CAR T cells is strongly associated with sustained therapeutic benefit. Achieving this persistence will likely separate clinically meaningful therapies from those that fall short. 

Soula expanded on this by highlighting the importance of the mechanism of action. Successful therapies may need to go beyond T-cell activation alone, instead engaging multiple components of the immune system. “The immune system is like an orchestra,” he explained. “While T cells are a key instrument, like a violin, the other instruments in the background are critical too; you cannot play a symphony with just violins.” Coordinated activity among different cell types is essential for optimal outcomes, highlighting the targeting and engagement of other immune cells as a potential parameter for success. 

Specificity and targeting precision will also remain central to both efficacy and safety, Soula emphasized.

Beyond biology, execution factors—including funding, expertise, and regulatory environment—will influence which programs succeed. Soula noted regional disparities in capital availability and clinical trial efficiency, with some companies increasingly looking to conduct trials in China to accelerate development timelines. 

Gill suggested that, initially, success is most likely in indications where ex vivo CAR T has already demonstrated efficacy, such as hematological malignancies. However, lower development costs could enable faster iteration and broader exploration of new targets.

 “I think there is still going to be a struggle with solid tumors,” he said. “But the cost of the trials should be lower, and so academia and biopharma should be able to iterate a lot faster.”  

Critical success factors in development: 

• Long-term CAR T persistence and durability. 

• Innovative, multi-cell immune engagement strategies. 

• Precise targeting and specificity. 

• Strong execution: funding, expertise, and regulatory strategy. 

The future of in vivo CAR T: Expansion, innovation, and new indications 

How do you see in vivo CAR T therapy evolving over the next 10 years? 

Over the coming decade, in vivo CAR T therapy is expected to expand rapidly across multiple dimensions. Tobin anticipates advances in vector engineering, particularly in improving targeting precision and integration site control. Combination strategies—pairing in vivo CAR T with vaccines or bispecific antibodies—may further enhance persistence and efficacy, particularly in heterogeneous tumors. 

“There are lots of different axes that in vivo CAR cell therapy is going to expand along.” — Dr. Jonathan Tobin 

Soula envisions a phased evolution, starting with validation of early clinical results, followed by improvements in manufacturability and cost. Advances in lentiviral vector production are expected to play a critical role, given the lack of historical demand for large-scale manufacturing in this area.  

The breadth of indications that in vivo CAR T therapy can address is also expected to expand, both Tobin and Soula highlighted. Beyond oncology, emerging data suggest potential applications in autoimmune diseases, challenging longstanding assumptions about disease mechanisms. 

“We haven’t yet seen a treatment that can actually cure so many diverse diseases.” — Dr. Rémi Soula 

Gill expects a new wave of innovation focused on enhancing the “chassis” of in vivo CAR T therapies. As researchers identify limitations of first-generation approaches, next-generation designs will incorporate additional genetic modifications to overcome these shortcomings. For example, modifications to T-cell fitness could improve the potency and persistence of the therapies. 

“As we learn what the deficiencies of the platform are, we’ll see additional innovations.” — Dr. Saar Gill 

Gill also suggested that efforts focused on improving ex vivo CAR T therapy may shift toward the in vivo modality, spurring additional innovations.  

Future directions shaping the field:  

• Advances in vector design and targeting precision. 

• Expansion into autoimmune and non-cancer indications. 

• Improved manufacturing scalability and affordability. 

• Development of next-generation engineered CAR T platforms. 

 

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