A biomimetic, non-genetic approach was explored to enhance CAR-T biodistribution by coating cells with red blood cell membrane–chimeric liposomes (Rlip). CAR-T cells were modified through simple incubation with Rlip to create Rlip-CAR-T constructs.
In vitro assessments evaluated coating stability, CD47-mediated resistance to macrophage uptake, preservation of CAR-T phenotype, and antigen-specific cytotoxic function. In vivo experiments examined biodistribution, tumor infiltration, and therapeutic efficacy in two models: Nalm-6 systemic leukemia and 1806-luc subcutaneous ovarian cancer.
Rlip coating reliably displayed CD47, reducing macrophage phagocytosis and extending peripheral persistence without perturbing memory subset composition, activation markers, or intrinsic cytotoxicity. In both hematologic and solid tumor settings, Rlip-CAR-T cells showed diminished off-target accumulation in liver, spleen, and lungs and enhanced intratumoral localization.
Leukemia model results demonstrated superior tumor control and longer survival with Rlip-CAR-T therapy compared with controls. Interpretation: This platelet-free, erythrocyte-mimetic surface engineering strategy non-genetically modifies CAR-T cells to simultaneously promote immune evasion and targeted tumor delivery, potentially improving distribution and efficacy across cancer types.
Uncertainty remains regarding long-term safety and translatability beyond preclinical models.
Frontiers in Immunology published a clinical update in Infectious Disease on 02 Apr 2026.
The item focuses on Erythrocyte membrane–liposome coating sustains circulation stability and targeted tumor therapy of CAR-T cells.
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