While mice are not people (except for my dear Ed!!!) and ratties are - mice usually take on our troubles first!!! Though not everything that helps the mice, helps the rattie...it is a start....
Enhanced
cytotoxicity of reovirus and radiotherapy in melanoma cells is mediated through
increased viral replication and mitochondrial apoptotic signaling. Gráinne, Kyula
, Mansfield, et al. Oncotarget, July,
2016.
"Oncolytic viruses selectively target and replicate in cancer
cells, providing us with a unique tool with which to target and kill tumour
cells. These viruses come from a diverse range of viral families including
reovirus type 3 Dearing (RT3D), a non-pathogenic human double-stranded RNA
oncolytic virus, which has been shown to be an effective therapeutic agent,
both as a mono-therapy and in combination with traditional chemotherapeutic
drugs. This study investigated the interaction between RT3D and radiotherapy in
melanoma cell lines with a BRAF mutant, Ras mutant or BRAF/Ras wild type
genotype. The data indicates that RT3D combined with radiotherapy significantly
increased cytotoxicity relative to either single agent, independent of
genotype, both in vitro and in vivo. The mechanism of
enhanced cytotoxicity was dependent on an increase in viral replication,
mediated by CUG2 up-regulation and subsequent down-regulation of pPKR and
p-eIF2α, leading to the activation of mitochondrial apoptotic signaling resulting
in increased cell death."
As noted in an article in
Oncology Network
regarding this study:
Radiotherapy supercharges cancer targeting viruses to treat melanoma the editor notes,
"The findings show that combining oncolytic viruses with radiotherapy could be an exciting new way to treat melanoma. Reoviruses are common viruses that are generally harmless to normal cells, but they can be deadly to cancer. Previous research has shown that the oncolytic virus RT3D is
resistant to high doses of radiation, and so could be used with
radiotherapy to treat skin cancers like melanoma. Researchers at the ICR and The Royal Marsden treated melanoma cells
using combinations of radiotherapy and RT3D, to investigate their
effects on cellular mechanisms in melanoma. The RT3D virus showed higher replication rates in melanoma when used
with radiotherapy, helping it to kill more cancer cells than either
treatment separately."
Thanks, to Linda Dylla for sharing this report. For what it's worth.
Then there's this:
Eradication of large established tumors in mice by
combination immunotherapy that engages innate and adaptive immune responses. Moynihan, Opel, Szeto, et al.
Nat Med. 2016 Oct 24.
Checkpoint blockade with
antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or
programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor
regression in metastatic cancer, but these dramatic responses are confined to a
minority of patients. This suboptimal outcome is probably due in part to the
complex network of immunosuppressive pathways present in advanced tumors, which
are unlikely to be overcome by intervention at a single signaling checkpoint.
Here we describe a combination immunotherapy that recruits a variety of
innate and adaptive immune cells to eliminate large tumor burdens in syngeneic
tumor models and a genetically engineered mouse model of melanoma; to our
knowledge tumors of this size have not previously been curable by treatments
relying on endogenous immunity. Maximal antitumor efficacy required four
components: a tumor-antigen-targeting antibody, a recombinant interleukin-2
with an extended half-life, anti-PD-1 and a powerful T cell vaccine.
Depletion experiments revealed that CD8+ T cells, cross-presenting
dendritic cells and several other innate immune cell subsets were required for
tumor regression. Effective treatment induced infiltration of immune cells and
production of inflammatory cytokines in the tumor, enhanced antibody-mediated
tumor antigen uptake and promoted antigen spreading. These results demonstrate
the capacity of an elicited endogenous immune response to destroy large,
established tumors and elucidate essential characteristics of combination
immunotherapies that are capable of curing a majority of tumors in experimental
settings typically viewed as intractable.
Whew!!! Melanoma Big Dogs have been saying (and I've been reporting here) that combo's are the wave of future melanoma treatment. This study is certainly throwing it all at 'em!!! Side effects here we come! But....if it works....
- c