This article is the comprehensive summary of our Morningglorysciences Summer Beginner Series on “In vivo CAR-T.” Previous articles covered the basics, leading researchers and companies, technical challenges, and global partnerships. Here, we revisit the entire field and place In vivo CAR-T in the broader context of immunotherapy.
Introduction｜Why In vivo CAR-T Matters
Conventional CAR-T therapy has relied on “ex vivo” approaches—extracting T cells from patients, genetically modifying them, and reinfusing them. This process is costly, complex, and capacity-limited.
In vivo CAR-T addresses these challenges by enabling gene modification directly inside the patient’s body, potentially reducing cost and increasing accessibility.
Chapter 1｜The Rise and Limits of CAR-T Therapy
CAR-T therapy revolutionized the treatment of hematologic cancers but has struggled in solid tumors due to the tumor microenvironment and antigen heterogeneity. Moreover, high costs, individualized production, and limited patient access have restricted its broader impact.
Chapter 2｜Technological Foundations of In vivo CAR-T
The foundation of in vivo CAR-T lies in delivering genetic instructions directly into patients. Key technologies include:
- Vector systems: Retrovirus, lentivirus, AAV, and lipid nanoparticles (LNPs)
- Targeting specificity: Selective delivery to T cells
- Safety switches: On/off control mechanisms
mRNA-LNP, made famous by COVID-19 vaccines, is also a promising platform for In vivo CAR-T. Directly inducing CAR-T cells inside patients could bypass traditional manufacturing entirely.
Chapter 3｜Key Institutions and Companies
Major players in In vivo CAR-T research include:
- Academia: University of Pennsylvania, Stanford, MD Anderson
- Biotechs: Capstan Therapeutics, Kyverna, Intellia
- Pharma: Novartis and BMS via partnerships
Capstan Therapeutics is particularly notable for its pioneering work in mRNA-LNP-based In vivo CAR-T development.
Chapter 4｜Recent Advances (Past 5 Years)
Since 2019, multiple preclinical studies have demonstrated efficacy of in vivo CAR-T, especially in hematologic cancers. Solid tumor applications are expanding, and regulators such as the FDA are signaling readiness for accelerated pathways in this innovative space.
Chapter 5｜Market Trends and Investment Landscape
The global cell therapy market is projected to reach multi-trillion yen scale by 2030. In vivo CAR-T is positioned as the “second generation” of cell therapy, attracting strong VC investment. Many U.S. biotechs are pursuing platform business models, combining mRNA and gene editing technologies.
Chapter 6｜Challenges and Future Outlook
Remaining challenges include:
- Improving gene delivery efficiency
- Reducing off-target effects
- Establishing long-term safety data
- Standardization of manufacturing and regulation
Despite these hurdles, In vivo CAR-T could fundamentally change cancer treatment. The vision of “vaccination-like therapies” where immune cells are engineered inside patients may soon become reality.
Next in the Series
Next, we will publish the grand summary of the Summer Beginner Series in two parts, integrating anti-obesity drugs, ADCs, In vivo CAR-T, and bispecific antibodies. This will serve as the bridge from beginner to intermediate/advanced understanding.
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This article was edited by the Morningglorysciences team.
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