Department of Anesthesiology, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Hum Vaccin Immunother. 2023 Aug;19(2):2262639. doi: 10.1080/21645515.2023.2262639. Epub 2023 Oct 3.
Schwannomas are slow-growing benign peripheral nerve sheath tumors derived from Schwann-lineage cells that develop in association with NF2-related schwannomatosis (NF2) and schwannomatosis (NF3), as well as spontaneously. Individuals affected with NF2 and NF3 have multiple schwannomas with tumors arising throughout life. Surgical resection, the standard management, is limited in scope and efficacy and is itself associated with significant morbidity. We have previously shown that direct intratumoral injection of attenuated Typhimurium (. Typhimurium), strain VNP20009, showed a potent anti-tumor effect in preclinical NF-2 schwannoma models. The United States Federal Drug Administration (FDA) requires that bacterial products utilized in clinical trials be produced without exposure to animal-derived-products. In this context, we developed, characterized, and tested the antitumor efficacy of an attenuated . Typhimurium serially passaged in animal-product-free media, naming it VNP20009-AF for "VNP20009-animal-product-free." Our in vitro data did not indicate any significant changes in the viability, motility, or morphology of VNP20009-AF, compared to its parental strain. In vivo efficacy data demonstrated that VNP20009-AF and VNP20009 controlled tumor growth to the same degree in both human NF2-schwannoma xenograft and murine-NF2 schwannoma allograft models. Together, these data support the use of VNP20009-AF for the translation of bacterial schwannoma therapy into clinical trials.
施万细胞瘤是一种生长缓慢的良性周围神经鞘肿瘤，来源于许旺细胞谱系细胞，与 NF2 相关的神经鞘瘤病（NF2）和神经鞘瘤病（NF3）以及自发性相关。患有 NF2 和 NF3 的个体有多个神经鞘瘤，肿瘤在一生中发生。手术切除是标准的治疗方法，但范围和疗效有限，本身也与显著的发病率有关。我们之前已经表明，在临床前 NF-2 神经鞘瘤模型中，向肿瘤内直接注射减毒鼠伤寒沙门氏菌（ Typhimurium），菌株 VNP20009，具有很强的抗肿瘤作用。美国食品和药物管理局（FDA）要求在临床试验中使用的细菌产品在生产过程中不接触动物源性产品。在这种情况下，我们开发、表征和测试了在无动物产品培养基中连续传代的减毒鼠伤寒沙门氏菌 VNP20009 的抗肿瘤功效，并将其命名为 VNP20009-AF，意思是“VNP20009-无动物产品”。与亲本菌株相比，我们的体外数据没有表明 VNP20009-AF 的活力、运动性或形态有任何显著变化。体内疗效数据表明，VNP20009-AF 和 VNP20009 在人 NF2 神经鞘瘤异种移植和鼠 NF2 神经鞘瘤同种异体移植模型中都能以相同的程度控制肿瘤生长。这些数据共同支持使用 VNP20009-AF 将细菌神经鞘瘤治疗转化为临床试验。
