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Unconventional Case Study of Neoadjuvant Oncolytic Virotherapy for Breast Cancer

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.

Clinical studies for each OVT, equally as for any novel cancer treatment, always start in group of patients with metastatic disease who have already passed many rounds of chemotherapy, radiotherapy and/or immunotherapy, and who therefore often have a compromised immune system and overall health status. The therapy utilized attenuated measles and vesicular stomatitis virus preparations that were not of clinical grade, but were made in the patient’s laboratory and used as clarified cell culture supernatants, devoid of extensive purification from host–cell nucleic acids and proteins. Although current knowledge [ 10] does not imply that anti-viral neutralizing antibodies prevent intratumoural efficacy of OVT, to minimize such a possibility, we exploited a sequential virotherapy strategy in which treatment was initiated using MeV and was switched later to another virus – VSV, after three weeks of therapy.

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