复发性乳腺癌新辅助溶瘤病毒疗法的非常规病例研究

An Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Recurrent Breast Cancer.

作者信息

Forčić Dubravko, Mršić Karmen, Perić-Balja Melita, Kurtović Tihana, Ramić Snježana, Silovski Tajana, Pedišić Ivo, Milas Ivan, Halassy Beata

机构信息

Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, 10000 Zagreb, Croatia.

Centre of Excellence for Virus Immunology and Vaccines, 10000 Zagreb, Croatia.

出版信息

Vaccines (Basel). 2024 Aug 23;12(9):958. doi: 10.3390/vaccines12090958.

Abstract

Intratumoural oncolytic virotherapy may have promise as a means to debulk and downstage inoperable tumours in preparation for successful surgery. Here, we describe the unique case of a 50-year-old self-experimenting female virologist with locally recurrent muscle-invasive breast cancer who was able to proceed to simple, non-invasive tumour resection after receiving multiple intratumoural injections of research-grade virus preparations, which first included an Edmonston-Zagreb measles vaccine strain (MeV) and then a vesicular stomatitis virus Indiana strain (VSV), both prepared in her own laboratory. The intratumoural virus therapy was well tolerated. Frequent imaging studies and regular clinical observations documenting size, consistency and mobility of the injected tumour demonstrate that both the MeV- and VSV-containing parts of the protocol contributed to the overall favourable response. Two months after the start of the virus injections, the shrunken tumour was no longer invading the skin or underlying muscle and was surgically excised. The excised tumour showed strong lymphocytic infiltration, with an increase in CD20-positive B cells, CD8-positive T cells and macrophages. PD-L1 expression was detected in contrast to the baseline PD-L1-negative phenotype. The patient completed one-year trastuzumab adjuvant therapy and remains well and recurrence-free 45 months post-surgery. Although an isolated case, it encourages consideration of oncolytic virotherapy as a neoadjuvant treatment modality.

摘要

肿瘤内溶瘤病毒疗法有望成为一种手段,用于缩小无法手术切除的肿瘤体积并降低其分期,为成功手术做准备。在此,我们描述了一个独特的病例,一名50岁的女性病毒学家,患有局部复发性肌肉浸润性乳腺癌,她在接受多次肿瘤内注射研究级病毒制剂后,能够进行简单的非侵入性肿瘤切除。这些病毒制剂首先包括埃德蒙斯顿-萨格勒布麻疹疫苗株(MeV),然后是水疱性口炎病毒印第安纳株(VSV),均在她自己的实验室制备。肿瘤内病毒疗法耐受性良好。频繁的影像学研究和定期的临床观察记录了注射肿瘤的大小、质地和活动度,表明方案中含MeV和VSV的部分均对总体良好反应有贡献。开始病毒注射两个月后,缩小的肿瘤不再侵犯皮肤或下方肌肉,遂进行手术切除。切除的肿瘤显示出强烈的淋巴细胞浸润,CD20阳性B细胞、CD8阳性T细胞和巨噬细胞增加。与基线时PD-L1阴性表型相反,检测到了PD-L1表达。患者完成了为期一年的曲妥珠单抗辅助治疗,术后45个月情况良好且无复发。尽管这是一个孤立的病例,但它促使人们考虑将溶瘤病毒疗法作为一种新辅助治疗方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0ca/11435696/91c80fbc831a/vaccines-12-00958-g001.jpg

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