In vivo CAR-T: immunotherapy without the lab

By Ana Espino | Published on March 4, 2026 | 3 min read


CAR-T cell therapy has transformed the management of certain hematologic malignancies. Traditionally, however, its development relies on a complex procedure: harvesting a patient’s T lymphocytes, genetically modifying them in the laboratory, expanding the cells, and reinfusing them. This lengthy, costly, and technically demanding process limits access to treatment and creates major logistical constraints. In this context, direct in vivo generation of CAR-T cells—without ex vivo manipulation—emerges as an innovative strategy that could reshape cellular immunotherapy.  

A 2025 review published in Human Vaccines & Immunotherapeutics examines recent advances in this emerging approach. The authors aim to summarize gene-delivery platforms capable of modifying T lymphocytes directly within the body, as well as the available preclinical and clinical evidence.  

Can CAR-T cells be created directly in the body?  

Unlike the conventional strategy, in vivo CAR-T therapy involves administering vectors that can specifically target T lymphocytes and deliver the gene encoding the chimeric antigen receptor (CAR). Several systems are being explored:
  

• Viral vectors, especially lentiviruses and adeno-associated viruses (AAV), which offer high transduction efficiency.
• Non-viral vectors, such as lipid nanoparticles (LNPs), polymers, or exosomes, enabling transient and potentially more controllable expression.

 
The authors also describe the evolution of CAR designs up to fifth-generation CARs, incorporating co-stimulatory domains and cytokine-signaling modules intended to improve persistence and antitumor activity.  

Preclinical models have shown that these approaches can generate functional CAR-T cells directly in vivo, with significant antitumor activity, particularly in leukemia and lymphoma models. Early clinical data, although limited, suggest promising efficacy with an acceptable safety profile.  

Toward simpler, more accessible CAR-T  

Despite meaningful progress, several major challenges still determine large-scale clinical translation. The safety of gene-delivery vectors remains a top priority, particularly regarding the risk of uncontrolled genomic integration associated with certain viral vectors. Fine control over transgene expression, limiting off-target effects, and managing the duration of activity of modified cells are key issues to ensure an optimal benefit–risk profile.  

Non-viral platforms such as LNPs offer attractive safety prospects, but they still need improvements in T-cell–specific targeting and intracellular delivery efficiency to reach yields comparable to viral systems.  

In addition, extending in vivo CAR-T to solid tumors is a major biological challenge. The immunosuppressive tumor microenvironment, antigen heterogeneity, and T-cell functional exhaustion currently limit persistence and antitumor efficacy. Combining strategies—precision genome editing, microenvironment modulation, and AI-assisted optimization of vectors and antigen targets—could help overcome these barriers.  

Thus, while in vivo CAR-T therapy is still in technological maturation, it represents a potentially transformative evolution of cellular immunotherapy. By simplifying production, reducing delays, and expanding accessibility, it could redefine therapeutic standards—provided it is rigorously validated clinically and delivery platforms are fully secured.   

Read next: Immunotherapy on hold?

About the author – Ana Espino
PhD in Immunology, specialized in Virology  
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.