1482 <i>In-vivo</i> CAR-T cells produced by specific virus in refractory B cell lymphoma

<h3>Background</h3> More than ten autologous CAR-T cell products have been approved for the treatment of relapsed or refractory hematological malignancies, but still some patients cannot benefit due to the complex manufacture, high cost or rapid disease progression. <h3>Methods</h3> To tackle this dilemma, researchers developed <i>in-vivo</i> CAR-T cell therapy using specific virus or mRNA to explore the universally ‘off-the-shelf’ product. <h3>Results</h3> Here, we reported the first-in-human, investigator-initiated clinical trial, to evaluate the safety and efficacy of <i>in-vivo</i> CAR-T cells targeted CD19 generated from specific virus in patients with B-cell non-Hodgkin’s lymphoma (figure 1). A 64-year-old male patient with relapsed/refractory diffuse large B-cell lymphoma achieved a partial remission on day 35 after infusion with specific virus induced <i>in-vivo</i> CAR-T cells. The expansion peak of CAR-T cells <i>in vivo</i> was observed on day 17 days after treatment. The major side effects were myelotoxicity and grade 1 of cytokine release syndrome. No neurotoxicity or infection was observed. <h3>Conclusions</h3> To our knowledge, this was the first report demonstrated <i>in-vivo</i> CAR-T cells produced significant anti-tumor ability in patients with B-NHL. These data validate and support the efficacy and safety of <i>in-vivo</i> CAR-T cells in preclinical and clinical trials, providing a paradigm shift in the field of CAR-T cell therapies.