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Case Reports
. 2024 Aug 23;12(9):958.
doi: 10.3390/vaccines12090958.

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

Dubravko Forčić  1   2 , Karmen Mršić  3 , Melita Perić-Balja  4 , Tihana Kurtović  1   2 , Snježana Ramić  4 , Tajana Silovski  5 , Ivo Pedišić  6 , Ivan Milas  7 , Beata Halassy  1   2
Affiliations
Case Reports

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

Dubravko Forčić et al. Vaccines (Basel). .

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.

Keywords: Edmonston-Zagreb; breast cancer; measles virus; oncolytic virotherapy; vesicular stomatitis virus.

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Conflict of interest statement

BH has become a consultant of Vyriad in 2021. The work described in this paper contains the subject matter of European patent application No. PCT/EP2021/080992 filed on 8 November 2021. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Oncolytic virotherapy (OVT) protocol and outcomes. (A) OVT time-course showing timepoints of each individual virus administration (blue arrows for MeV and green ones for VSV) in relation to outcomes monitored as changes in tumour size (red symbols) and virus-specific neutralizing antibody titers (NT) (blue and green circles for anti-MeV and anti-VSV NT, respectively). (B) Details on viruses used for each application; CCID50-cell culture infective dose 50.
Figure 2
Figure 2
Imaging evidence of the effect of oncolytic virotherapy (OVT). (A) Changes in the ultrasound images of the treated tumour made at the same ultrasound system in the same position; representative images with tumour dimensions taken at the beginning and at the end of the therapy, and on day 8 when the worst clinical and ultrasound picture of the tumour size was noted. (B) Histopathological analysis of the tumour bed after OVT (three independent tumour sections) shows a histological picture of significant fibrosis, rich in immune cells, and without the presence of malignant cells. (C) Immunochemical staining of representative tumour sections before and after OVT, with anti-CD3, anti-CD8, and-CD4, anti-CD20, anti-PD-L1, anti-CD56 and anti-CD68 antibodies. Brown-black dots indicate positive staining. Tumour sections demonstrating an increase in expression of respective surface marker after OVT are denoted in red. Overall changes in each marker expression (in percentages) were evaluated in relation to entire tissue section, except for PD-L1 expression, which was evaluated according to the criteria for triple-negative breast cancer (immune cells only in the intratumoural and peritumoural areas were considered).
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