The next era of cell therapy

From ex vivo success to in vivo ambition

Ex vivo CAR-T therapies have achieved durable remission, and in some cases cure, in hematologic malignancies. Yet their success also exposed the accessibility limits of individualized manufacturing. High cost, long production timelines, and logistical complexity restrict access and prevent scale.

In vivo CAR-T approaches aim to convert the body itself into the manufacturing site. Rather than shipping cells across continents, viral vectors or nanoparticles deliver genetic instructions or mRNA directly to immune cells inside the patient. This paradigm promises off-the-shelf availability, outpatient delivery, and a fundamentally different economic model. But promise alone does not guarantee translation.

The commentary by Adrian Bot and Xianghong Li, along with my conversation with Shon Green, captures both the excitement and the caution surrounding this modality [1]Bot A, Li X. In vivo chimeric antigen receptor (CAR) therapy: quo vadis? Cell Gene Ther. Insights 2026; 12(1), 87–92. [2]Green S. The next frontier of in vivo CAR-T: a conversation with Shon Green. Cell Gene Ther. Insights 2026; 12(1), 15–22. . Early clinical signals show that in vivo CAR-T generation can achieve meaningful biological effects, yet the field must confront unresolved questions: genomic integration risk, dosing control, redosing feasibility, immunogenicity, and long-term persistence. What becomes clear is that in vivo CAR-T is not simply a new tool – it represents a new category of medicine that demands new frameworks for modeling, analytics, and clinical evaluation.

Manufacturing as the new bottleneck

If the first wave of in vivo cell therapy was constrained by biology, the second wave is constrained by manufacturing maturity. Dehui Kong’s analysis of CMC considerations makes a critical point: scalability is not an afterthought; it is the rate-limiting step. Both viral vectors and non-viral mRNA-LNP systems face persistent challenges related to production complexity, cost, and regulatory burden [3]Kong D. CMC considerations on in vivo CAR-T. Cell Gene Ther. Insights 2026; 12(1), 1–5. . She argues that CMC maturity, rather than biological feasibility, may be the decisive factor shaping in vivo CAR-T platforms.

For ex vivo allogeneic cell therapies, cryopreservation and post-thaw functional stability represent an additional, often underappreciated manufacturing constraint, as described by Jason Acker [4]Acker J. XX Cell Gene Ther. Insights 2026; 12(1), XX. Without reliable preservation strategies that maintain potency across storage, transport, and clinical deployment, even scalable production risks collapsing at the final translational step.

Reagan Jarvis reframes these challenges as one of systemization. The future success of cell therapies depends less on incremental scientific breakthroughs and more on disciplined integration of discovery and manufacturing [5]Jarvis R. XX Cell Gene Ther. Insights 2026; 12(1), XX. Shon Green’s interview echoes this reality from a developer’s perspective: analytics, potency assays, and comparability frameworks remain immature for in vivo CAR-T products. Without robust measurement systems, even the most elegant platforms risk regulatory and translational stagnation [2]Green S. The next frontier of in vivo CAR-T: a conversation with Shon Green. Cell Gene Ther. Insights 2026; 12(1), 15–22. .

Safety & supportive infrastructure

As cellular therapies grow more powerful, supportive care becomes a central enabling technology. Liam Tremble and Paula Maguire’s review reminds us that CRS, ICANS, and other therapy-induced toxicities are not peripheral complications; they are predictable consequences of immune activation [6]Tremble L, Maguire P. Role of supportive care in the future of cell therapies. Cell Gene Ther. Insights 2026; 12(1), 81–86.. Supportive care innovation is therefore not separate from therapeutic progress; it is a prerequisite for it. Regulatory frameworks, incentives, and dedicated drug development pathways must evolve in parallel with cell therapy innovation.

Solid tumors & beyond oncology

Arnaud Deladeriere argues that the persistent challenges of CAR-T and related modalities in solid tumors reflect not only biological barriers but also translational and systemic shortcomings [7]Deladeriere A. XX Cell Gene Ther. Insights 2026; 12(1), XX. Durable success in solid tumors will require integrated strategies that align biological design with manufacturability, intellectual property frameworks, and commercial realism.

While oncology remains the proving ground, the most transformative implications of CAR-T may lie beyond cancer. Autoimmune disease, fibrosis, metabolic disorders, and allergy represent emerging frontiers where immune reset strategies could redefine chronic disease management. Several authors emphasize that transient immune reprogramming may be sufficient to induce durable remission without lifelong treatment. This reframes cell therapy from a last-resort oncology intervention into a platform technology for systemic disease modification.

China Biotech ecosystems & convergence

Two interviews in this issue explore how geopolitical and ecosystem differences shape innovation trajectories. In my conversation with Zhenghong Gao, he highlights China’s biotech landscape as a complementary model optimized for rapid clinical translation and manufacturing scale [8]Gao Z. Leaping forward: how China’s biotech evolution is capturing the in vivo CAR-T frontier. Cell Gene Ther. Insights 2026; 12(1), 7–12.. Investigator-initiated trial frameworks, regulatory agility, and coordinated infrastructure enable faster iteration and proof-of-concept generation.

Rather than framing East and West as competitors, both Zhenghong and Shon point toward a future defined by convergence. The USA and EU excel at high-risk pioneering science; China excels at rapid execution and scale. The global future of advanced therapies may depend on how effectively these strengths interact. In a field where development timelines span a decade and patient need is immediate, speed is not a luxury but an ethical obligation.

Epilogue

If this special issue carries a single message, it is this: the next era of cell therapy will be defined less by isolated breakthroughs and more by integration. Biology, manufacturing, analytics, regulatory strategy, and global collaboration must advance together. Fragmented innovation may not deliver scalable medicine.

The field is transitioning from a phase of heroic experimentation to one of disciplined construction. That transition is difficult but necessary. Success will depend on assembling scientific and industrial components into a coherent system capable of reaching patients everywhere, not only in specialized centers.

The science has already proven what is possible. The next challenge is proving what is practical. And that challenge is no less ambitious.

References

1. Bot A, Li X. In vivo chimeric antigen receptor (CAR) therapy: quo vadis? Cell Gene Ther. Insights 2026; 12(1), 87–92.  Crossref

2. Green S. The next frontier of in vivo CAR-T: a conversation with Shon Green. Cell Gene Ther. Insights 2026; 12(1), 15–22.  Crossref

3. Kong D. CMC considerations on in vivo CAR-T. Cell Gene Ther. Insights 2026; 12(1), 1–5.  Crossref

4. Acker J. The cryo-sensitivity of NK cells: overcoming post-thaw decline. Cell Gene Ther. Insights 2026; 12(1), 97–104.  Crossref

5. Jarvis R. Systemization is key to fulfilling T cell therapy’s promise in cancer. Cell Gene Ther. Insights 2026; 12(1), 105–109.  Crossref

6. Tremble L, Maguire P. Role of supportive care in the future of cell therapies. Cell Gene Ther. Insights 2026; 12(1), 81–86.  Crossref

7. Deladeriere A. Solid tumors and advanced therapies: why science alone will not deliver the cure. Cell Gene Ther. Insights 2026; 12(1), 155–162.  Crossref

8. Gao Z. Leaping forward: how China’s biotech evolution is capturing the in vivo CAR-T frontier. Cell Gene Ther. Insights 2026; 12(1), 7–12.  Crossref

Biography

Yu (Clay) Cao PhD is an accomplished scientific leader with over 15 years of experience in drug discovery and translational development. Currently serving as Vice President and Head of Drug Discovery at GenEditBio, Dr Cao leads cross-functional teams advancing cell and gene therapies across rare diseases, oncology, and neurodegenerative disorders. He has deep expertise in preclinical development, IND-enabling studies, and in vivo delivery technologies, with a strong track record of progressing novel cell and gene therapeutics from discovery to clinical stage. Prior roles include research leader roles at Tessera Therapeutics and Agios Pharmaceuticals, where he drove innovative programs in immuno-oncology and gene editing. Trained as an immunologist, Dr Cao holds a PhD in Immunology, with additional credentials from Harvard Business School and Johns Hopkins University. He actively contributes to the field as an advisor or leadership member of different non-profit organizations.

Yu (Clay) Cao, Vice President and Head of Drug Discovery, GenEditBio, Boston, MA, USA

AUTHORSHIP & CONFLICT OF INTEREST 

Contributions: The named author takes responsibility for the integrity of the work as a whole, and has given their approval for this version to be published.

Acknowledgements: None.

Disclosure and potential conflicts of interest: The author has no conflicts of interest.

Funding declaration: The author received no financial support for the research, authorship and/or publication of this article.

AI process statement: ChatGPT was used for language polishing by the author after initial human drafting of the editorial.

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Copyright: Published by Cell & Gene Therapy Insights under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Attribution: Copyright © 2026 Yu Cao. Published by Cell & Gene Therapy Insights under Creative Commons License Deed CC BY NC ND 4.0.

Article source: This article was written by the named author and reviewed by BioInsights’ Editorial team to ensure clarity and alignment with BioInsights’ editorial standards. 

Revised manuscript received: Feb 4, 2026.

Publication date: Feb 25, 2026.