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In vivo CAR-T Insights Series (7) — Evolution of CAR Design in Next-Generation CAR-T Cell Therapy


 

The design of chimeric antigen receptors (CARs) has evolved dramatically — transforming from early proof-of-concept molecules to advanced, programmable receptors that are redefining in vivo CAR-T therapy.

🔹 First-Generation CARs

Contained only the CD3ζ signaling domain, which could trigger T-cell activation but offered limited persistence and antitumor efficacy.

🔹 Second-Generation CARs

Integrated co-stimulatory domains such as CD28 or 4-1BB, markedly enhancing T-cell proliferation, cytokine release, and in vivo durability.

These architectures remain the foundation of most commercial CAR-T products today.

🔹 Third-Generation and Next-Generation CARs

Combine multiple co-stimulatory modules (e.g., CD28 + 4-1BB) and introduce switchable or dual-target CAR designs to improve safety and control.

Emerging platforms incorporate ON/OFF molecular switches and logic-gated CARs, enabling more precise and tunable immune responses.

⚡ Key Insight

Optimized CAR architecture is crucial for balancing activation, persistence, and safety.

In in vivo CAR-T cell development, advanced CAR designs — combined with efficient mRNA-LNP delivery systems — are key to achieving potent, controllable, and targeted immune activity.

🌟 Levostar’s in vivo CAR-T solutions

From mRNA plasmid design to LNP formulation, Levostar provides complete solutions for in vivo CAR-T research.

Our Ab-LNP technology enables targeted delivery — from ready-to-use standard products (e.g., LNP-CD3/5/8) to fully customized antibody conjugation services.

 Let’s accelerate the future of cell therapy — directly inside the body.