Scientists Develop Magnetic-Acoustic Actuated CAR-T Cell Robots for Precision Antitumor Immunotherapy

Although chimeric antigen receptor (CAR) T cell therapy has shown incredible success in treating hematological malignancies, its application in solid tumors is unsatisfactory owing to the harsh physical barriers and immunosuppressive microenvironment.The ideal CAR T therapy will require a novel armored CAR T cell engineered to navigate the circulatory system,penetrate tumor tissues, and survive in the harsh tumor microenvironment to exert an adequate immune effect.

Recently, a research team led by Prof.CAI Lintao at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences developed a CAR T cellbased microrobot (M-CAR T) with magnetic-acoustic sequential actuation that can autonomously navigate to tumor sites for cell immunotherapy by decorating CAR T with immunomagnetic beads using click conjugation.

The result was published inAdvanced Materialson 17 February.

Schematic illustration of magnetic-acoustic sequentially actuated M-CAR T microrobots for self-controllable guidance towards solid tumor and significant immunotherapy.(Image by SIAT)

In this strategy, a living CAR T cell microrobot based on magnetic-acoustic sequential actuation for self-controllable targeting and augmented antitumor immunotherapy in solid tumors by artificially decorating immunomagnetic beads via click conjugation.M-CAR Ts are capable of magnetic-acoustic actuation for precision tumor targeting and in-situ activation of antitumor immune responses.Immunomagnetic beads engineered CAR T microrobots (M-CAR T) demonstrated controllable anti-flow and obstacle avoidance movement and maintained an on-demand route under magnetic guidance.Meanwhile, M-CAR T exhibited distinctive acoustic manipulative properties over CAR T cell control and can actively penetrate into artificial tumor tissues under magnetic-acoustic sequential actuation.

“Sequential actuation endows M-CAR Ts with magnetically actuated anti-flow and obstacle avoidance capabilities as well as tumor tissue penetration driven by acoustic propulsion, enabling efficient migration and accumulation in artificial tumor models,”said Prof.CAI.

In animal models, sequentially actuated M-CAR Ts achieved long-distance targeting and accumulated at the peritumoral area under programmable magnetic guidance, and subsequently, acoustic tweezers actuated M-CAR Ts to migrate into deep tumor tissues, resulting in a 6.6-fold increase in accumulated exogenous CD8+CAR T cells compared with that with no actuation.“Ingeniously, anti-CD3/CD28 immunomagnetic beads stimulate infiltrated CAR T proliferation and activationin situ, significantly enhancing their antitumor immune efficacies,”said Dr.PAN.

M-CAR T microrobots maintain the bioactive properties of CAR T cells and are capable of magneticpropelled spatial targeting and acoustic-actuated tumor penetration to cope with vascular anti-flow and obstacles for migrating into a deep tumor.After entering tumor tissues, immunomagnetic beadsin situstimulated CAR T cells for efficient expansion and activation to overcome immunosuppressive tumor environments.

“Such sequential actuation-guided cell microrobot combines the merits of autonomous targeting and penetration of intelligent robots with in-situ immune activation of T cells,”said Dr.PAN Hong,the other corresponding author of this study, “and holds considerable promise for clinical precision immunotherapies of solid cancer.”

Schematic illustration of magnetic-acoustic sequentially actuated M-CAR T microrobots for selfcontrollable guidance towards solid tumor and significant immunotherapy.(Image by SIAT)