Introduction: Is In Vivo CAR-T the Next Evolution in Cellular Immunotherapy?
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment approaches for several haematological malignancies. However, conventional ex vivo CAR-T cell therapy continues to face operational challenges, including patient-specific cell collection, manufacturing timelines, logistical coordination and treatment accessibility.
In vivo CAR-T cell therapy is emerging as an alternative engineering approach that aims to generate CAR-expressing T cells directly inside the patient's body. By potentially reducing dependence on personalised cell manufacturing, this technology could change how cellular immunotherapies are developed, delivered and scaled.
The industry is already moving beyond preclinical exploration. For example, Umoja Biopharma has advanced its VivoVec-based in vivo CAR-T programmes into clinical development, while AbbVie completed its acquisition of Capstan Therapeutics in 2025, adding a targeted lipid nanoparticle-based in vivo CAR-T programme to its portfolio.
Industry references supplied with the study: Umoja Biopharma.
Against this background, SPER Market Research conducted an HCP perception study involving 25 oncologists across the United States and Europe to understand awareness, perceived clinical advantages, safety concerns and future adoption expectations surrounding in vivo CAR-T.
Study Objective & Respondent Profile
A focused physician-perception study exploring clinical potential, technology differentiation, safety considerations and anticipated adoption of in vivo CAR-T compared with ex vivo CAR-T.
What the research set out to understand
The study evaluated physician perceptions of in vivo CAR-T versus ex vivo CAR-T, focusing on clinical potential, therapeutic indications, technology differentiation, safety considerations and anticipated adoption.
25 oncologists surveyed
Total: 25 respondents (100%)
Haemato-oncology · Medical oncology · Cellular therapy · Paediatric oncology
Key Findings: What Do Oncologists Think About In Vivo CAR-T?
1. Physician Awareness and Clinical Expectations
Awareness of in vivo CAR-T is developing, although familiarity varies across the surveyed specialists.
Overall, 56% of respondents demonstrated moderate or high familiarity.
agreed or strongly agreed that in vivo CAR-T could become an alternative to conventional CAR-T in selected applications.
However, this optimism remains conditional on demonstrating comparable efficacy, response durability and acceptable safety.
2. Which Cancer Indications Offer the Greatest Potential?
Haematological malignancies emerged as the leading areas of perceived clinical opportunity.
B-cell non-Hodgkin lymphoma was the most frequently selected indication, followed by acute lymphoblastic leukaemia and multiple myeloma.
These results suggest that surveyed oncologists currently see greater near-term potential in haematological malignancies than in solid tumours. This is a perception finding, not evidence of established indication-specific efficacy.
3. Perceived Advantages of In Vivo CAR-T vs Ex Vivo CAR-T
Manufacturing and treatment logistics were the most frequently identified potential advantages.
The findings highlight an important industry opportunity: reducing the operational complexity associated with conventional CAR-T manufacturing.
If successfully translated into clinical practice, in vivo engineering could reduce dependence on individualised cell production and potentially simplify treatment delivery.
Nevertheless, actual improvements in turnaround time, manufacturing economics and accessibility will require clinical and commercial validation.
4. What Are the Major Safety and Technology Concerns?
Despite positive expectations, oncologists identified several important barriers to wider adoption.
Delivery specificity and off-target genetic modification represent particularly important concerns.
In vivo engineering requires therapeutic vectors or delivery systems to reach the intended immune-cell populations while limiting unintended exposure. Researchers are investigating viral vectors, targeted lipid nanoparticles and other delivery approaches to improve cellular specificity.
Additional considerations include biodistribution, vector immunogenicity, CAR expression control, persistence and the potential for unintended genetic modification.
Scientific reference supplied with the study: Nature Reviews Drug Discovery.
5. Can In Vivo CAR-T Improve Treatment Accessibility and Economics?
of surveyed oncologists agreed or strongly agreed that in vivo CAR-T could improve treatment economics and accessibility.
The perceived opportunity is linked to potentially reduced manufacturing requirements, simpler treatment logistics and improved scalability.
However, lower treatment costs should not be assumed. Vector production, delivery technology, quality control, clinical monitoring and regulatory requirements may introduce different cost considerations.
6. What Is the Future Adoption Potential?
Physicians reported encouraging future adoption expectations:
Regarding the next five to ten years:
The findings suggest that oncologists are more inclined to view in vivo CAR-T as a complementary technology initially rather than an immediate replacement for conventional CAR-T.
Industry Insights: What Is Driving In Vivo CAR-T Development?
The competitive landscape is increasingly shaped by delivery technology, manufacturing strategy, target-cell specificity and therapeutic application.
Two developments illustrate this shift:
Viral delivery approach
Umoja Biopharma's VivoVec platform is described in the study as using lentiviral delivery for in vivo CAR-T programmes.
Non-viral delivery approach
Capstan's targeted lipid nanoparticle approach represents a non-viral route for in vivo immune-cell engineering.
- Umoja Biopharma: Its VivoVec platform uses lentiviral delivery to generate CAR-T cells inside the patient. Its development strategy includes programmes targeting B-cell malignancies and multiple myeloma.
- AbbVie and Capstan Therapeutics: Capstan's targeted lipid nanoparticle technology represents a non-viral approach to delivering genetic material for in vivo immune-cell engineering.
Industry references supplied with the study: Umoja Biopharma; PR Newswire.
These approaches demonstrate that the competitive landscape is not defined by a single delivery technology. Different platforms are exploring viral and non-viral methods, each with distinct considerations for targeting, expression, safety and manufacturing.
For pharmaceutical and biotechnology companies, the next development priorities include:
- Improving targeted delivery to the intended T-cell populations.
- Establishing predictable CAR expression and persistence.
- Demonstrating acceptable CRS and ICANS profiles.
- Evaluating long-term safety and biodistribution.
- Establishing scalable manufacturing and commercially sustainable treatment economics.
Conclusion: What Will Determine the Future of In Vivo CAR-T?
The SPER Market Research HCP perception study highlights encouraging physician expectations for in vivo CAR-T cell therapy, particularly in haematological malignancies.
Manufacturing simplification, faster treatment initiation and potential accessibility improvements are important perceived advantages. However, off-target genetic modification, delivery consistency and long-term safety remain significant adoption considerations.
The future of this technology will depend on translating engineering advances into reproducible clinical outcomes, demonstrating durable efficacy and establishing viable regulatory, manufacturing and reimbursement pathways.
For pharmaceutical companies, investors and biotechnology developers, understanding oncologist perceptions alongside clinical pipeline developments can help identify emerging opportunities, technology gaps and adoption barriers in the evolving CAR-T landscape.
In vivo CAR-T could become an important complement to conventional cellular immunotherapy, but clinical validation, delivery precision and treatment economics will determine its long-term position in oncology.
In vivo CAR-T could become an important complement to conventional cellular immunotherapy, but clinical validation, delivery precision and treatment economics will determine its long-term position in oncology.
