肿瘤细胞治疗研究
英文原题：CCL19-armed oncolytic adenovirus synergizes with CCR7-expressing CAR-T cells to suppress ovarian tumor growth.
我们证明，体外扩增的 HER2 CAR-T 细胞中超过 80% 为 CCR7⁺ 细胞，可强效迁移至 CCL19。
实体瘤对嵌合抗原受体（CAR）T细胞疗法仍普遍耐药，主要原因是CAR-T细胞无法浸润肿瘤床。我们发现，体外扩增的HER2 CAR-T细胞中超过80%为CCR7+细胞，可强烈迁移至CCL19。缺失E1B-55 kDa的溶瘤腺病毒在保留完整溶瘤效力的同时，可表达并分泌具有生物活性的CCL19，使CAR-T细胞迁移增加3倍。在携带SKOV3卵巢肿瘤的NSG小鼠中，先进行两次瘤内oAd-CCL19注射，再静脉输注HER2-CAR-T细胞，可最有效抑制肿瘤生长，未见显著毒性，并伴随肿瘤内CAR-T细胞增加。因此，表达CCL19的溶瘤腺病毒可安全地将卵巢肿瘤转化为富含趋化因子的靶组织，招募CAR-T细胞，为实体瘤CAR-T治疗提供一种易于转化的策略。
Solid tumors remain refractory to chimeric antigen receptor (CAR) T cell therapy largely because they fail to infiltrate the tumor bed. We show that in vitro expanded HER2 CAR-T cells are more than 80% CCR7 + cells that migrate vigorously to CCL19. An E1B-55 kDa-deleted oncolytic adenovirus expressing CCL19 retained full oncolytic potency, secreted bioactive CCL19 and tripled CAR-T migration. In NSG mice bearing SKOV3 ovarian tumors, two intratumoral oAd-CCL19 injections followed by intravenous HER2-CAR-T cells achieved most effective inhibition of tumor growth without significant toxicity, accompanied by increased intratumoral CAR-T cells. Thus, CCL19-armed oncolytic adenovirus safely converts ovarian tumors into chemokine-rich targets that recruit CAR-T cells, providing a readily translatable strategy for solid-tumor CAR-T therapy.
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