Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer

Abstract

We reported earlier the delivery of antiangiogenic single chain antibodies by using oncolytic vaccinia virus strains to enhance their therapeutic efficacy. Here, we provide evidence that gene-evoked production of melanin can be used as a therapeutic and diagnostic mediator, as exemplified by insertion of only one or two genes into the genome of an oncolytic vaccinia virus strain. We found that produced melanin is an excellent reporter for optical imaging without addition of substrate. Melanin production also facilitated deep tissue optoacoustic imaging as well as MRI. In addition, melanin was shown to be a suitable target for laser-induced thermotherapy and enhanced oncolytic viral therapy. In conclusion, melanin as a mediator for thermotherapy and reporter for different imaging modalities may soon become a versatile alternative to replace fluorescent proteins also in other biological systems. After ongoing extensive preclinical studies, melanin overproducing oncolytic virus strains might be used in clinical trials in patients with cancer.

Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time

“…Optoacoustic (photoacoustic) imaging attracts growing interest from the biological and medical research communities, as manifested by the ever increasing number of publications encompassing variety of new applications that exploit the unique advantages offered by the technology [1][2][3][4][5] . In particular, the capacity to image spectrally distinctive photo-absorbing agents with high spatio-temporal resolution at depths far beyond the diffusive limit of light opens unprecedented capabilities for functional and molecular imaging [6][7][8][9][10] .…”

PEG-pHPMAm-based polymeric micelles loaded with doxorubicin-prodrugs in combination antitumor therapy with oncolytic vaccinia viruses

“…It should be taken into account in this regard, however, that at the viral doses used (5×10 6 pfu), both the control and the enzyme-expressing virus were already highly effective in inhibiting tumor growth: as exemplified by Fig. 6B-D, even in the absence of DOX-or pg-micelle-cotreatment, tumor volumes never exceeded 200%, confirming the strong oncolytic potential of vaccinia viruses [21][22][23][24][25][26][27] . Interestingly, when combined with free DOX, the oncolytic activity of GLV-1h190 was somewhat reduced (Fig.…”

“…In a number of studies, it was shown that recombinant vaccinia viruses (rVACV) derived from the Lister-strain are effective in treating different solid tumor types (reviewed in 21 ). Monitoring of the successful tumor colonization and the therapeutic effects can be performed by different imaging modalities, including optical 24 , optoacoustic 25 , PET- 26,27 , and by MR-imaging 25 . Reporter gene-encoding rVACV can therefore be considered theranostic agents [28][29][30] .…”

Vaccinia Virus-Mediated Expression of Transcription Factor Klf4 Enhances Oncolytic Virotherapy of Colorectal Cancer

“…We previously reported on the tumor selectivity and anti-tumoral efficacy of the replication-competent vaccinia virus strain GLV-1h68 in a broad variety of human tumor xenograft models [15]. More recently, we demonstrated the functional applicability of "second-generation" recombinant vaccinia virus (rVACV) strains expressing therapeutical payloads such as anti-VEGF single-chain antibodies targeting tumor angiogenesis and radio sensitization of the tumor-associated vasculature [16,17], the human sodium iodide symporter (hNIS) [18], enzymes for the synthesis of melanin for optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer [19] or bone morphogenetic protein-4 (BMP4) in an orthotopic glioblastoma model [20].…”