Injectable bioinstructive microfoam for rapid bedside/in vivo programming of CAR-T cells

While chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of hematological malignancies and are being explored for solid tumors, their widespread use remains limited by high costs, complex manufacturing requirements, long wait times, and unequal access. Here, we describe a methylcellulose-based gene therapy microfoam that enables rapid generation of CAR-T cells for subcutaneous administration within hours of blood collection. Specifically, we demonstrate that colocalization of T cells and vector within the foam promotes efficient CAR gene transfer. Following subcutaneous injection, newly programmed CAR-T cells disperse systemically and mediate regression of distal tumors in mouse xenograft models of lymphoma and hepatocellular carcinoma, with antitumor activity comparable to conventionally manufactured CAR-T cells. The platform operates as a sterile closed system and does not require prolonged cell culture, centralized manufacturing facilities, or cleanroom-based cell production. These findings establish proof of concept for a simplified CAR-T generation strategy that may reduce manufacturing complexity and infrastructure requirements relative to conventional CAR-T therapy while improving the accessibility of cellular immunotherapies.