Før Solux og andre begynner å latterliggjøre dette kan vi iallefall fastslå at et internasjonalt fagtidsskrift ikke aksepterer artikler om bagateller eller uinteressante ting. Så er det selvsagt slik at in vivo ikke er det samme som en klinisk test på mennesker, men den som skal tolke dette som noe annet enn positivt skal iallefall ha god fantasi…
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Fra melanoma cohort 1 med 3 injeksjoner:
In patient 4 there was an apparent response in both the primary and non-injected tumours, a so-called ‘abscopal effect’.
Tilfeldig? I think not!
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Først en complete response og nå en abscopal effect så tidlig i studien.
Nei, dette er ikke tilfeldig! 
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Her er abstraktet:
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25501
Men: First published: 13 May 2019?
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Den er kategorisert som ikke informasjonspliktig pressemld. Merkelig. Hva er da informasjon pliktig?
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Synes timingen på meldingen er perfekt ifht. hvor vi ligger teknisk for en rekyl 
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First published (13. mai) er kanskje dato da artikkelen er skrevet, utgivelsen av denne Journal skjer månedlig.
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Results
We have previously shown that ONCOS-102 treatment followed by three doses of pembrolizumab can slow or halt the growth of the A2058, A375, and SK-MEL-2 melanoma tumor nodules in humanized mice. This schedule of the combination therapy induced a reduction in the untreated left tumor volumes in the SK-MEL-2 tumor-bearing hu-NOG mouse group but not in the A375 tumor-bearing hu-NOG mouse group (unpublished data).
To potentially induce an abscopal effect against A2058-tumor-bearing hu-NOG mice, the dosing schedule of the combination therapy of ONCOS-102 and pembrolizumab was
revised so that both agents were administered on days 15, 17, and 19 with continuation of pembrolizumab administration every 3 to 4 days thereafter (Figure 1, Table 1). On day 26, the mean tumor volumes (MTVs; Figure 1B and D) of the group 2 of both tumors intratumorally treated with ONCOS-102 was 113,45 mm3 and was lower than mice treated intravenously with pembrolizumab (either 200 µg or 400 µg, group 3 and 4) respectively 162,75 and 138,58 mm3 (Figure 1B and D). The MTV of the PBS-injected tumors of the vehicle were 157,95 mm3 (group 1)
On day 26, the mean tumor volumes (MTVs; Figure 1B and D) of the group 2 of both tumors intratumorally treated with ONCOS-102 was 113,45 mm3 and was lower than mice treated intravenously with pembrolizumab (either 200 µg or 400 µg, group 3 and 4) respectively 162,75 and 138,58 mm3 (Figure 1B and D). The MTV of the PBS-injected tumors of the vehicle were 157,95 mm3 (group 1).
Tumors on the mice with the right tumor treated with the virus intratumorally plus pembrolizumab intravenously (either 200 µg or 400 µg, group 5 and 6) were modestly greater (respectively 147 and 124,48 mm3) than the MTV of the ONCOS-102 treated mice (113, 45 mm3, group 2). Instead, the untreated tumors (left flank) on the hu-NOG mice with the right tumors treated with ONCOS-102 followed by pembrolizumab (either 200 µg or 400 µg, group 5 and 6) were smaller (respectively 108,71 and 82 mm3) than the MTV of the mice treated with the right tumors in the same group (respectively 147 and 124,48 mm3) and MTV of the ONCOS-102 treated groups (113,45 mm3, group 2). The difference between the MTVs among the groups were not statistically significant.
On day 40, the MTV of the right treated tumors (group 5 and 6) were larger (respectively 207,86 and 172 mm3) than tumor volumes of the untreated left tumors on the same hu-NOG mice (respectively for group 5 and 6: 172,43 and 111,4 mm3). Untreated tumors from these groups were also smaller than the MTVs of the mice treated with ONCOS-102 into two tumors (183,15 mm3, group 2). The treatment with pembrolizumab only (either 200 µg or 400 µg, group 3 and 4) was less effective than virus alone or combinatory therapies (ONCOS-102 and pembrolizumab) (Figure 1C and E). The differences between MTVs among groups were not statistically significant.
Discussion
A major goal of immunotherapy is induction of an abscopal effect so that all tumour lesions including distant metastases are reduced or eliminated. We have shown that three intratumoral treatments with the oncolytic adenovirus ONCOS-102 followed by three
ystemic doses of pembrolizumab can slow or halt the growth of the A205826, A375, and SK-MEL-2 melanoma tumor nodules in humanized mice (unpublished data). This schedule of the combination therapy induced a reduction in the untreated left tumor volumes in the SK-MEL-2 tumor-bearing hu-NOG mouse group but not in the A375 tumor-bearing hu-NOG mouse group (data unpublished). Here, we showed that a modified dosing schedule of the combination, beginning the CPI concurrently with the oncolytic viral therapy and continuing the CPI treatment, appeared to induce an abscopal effect in the untreated left tumor nodules of the same size in a humanized A2058 melanoma model.
Several animal studies using different combination therapies and treatment regiments have studied abscopal effect. A study of combination therapy comprised of oncolytic vaccinia Western Reserve strain and anti-PD1, anti-CTLA-4, or Oxaliplatin showed an abscopal effect in untreated MCA205 Ifnar-/- tumors.28 Interestingly, the timing of a single administration of the CPI at 7 days post oncolytic virus treatment significantly increased the efficacy of the combination therapy against the MCA205 wt tumor cells in vivo.28 The probability and effect size of the abscopal effect was maximized by using the tumor variant which was most susceptible to the oncolytic WR virus (MCA205Ifnar-/-), delayed tumor inoculum for the contralateral untreated tumor nodules, and oncolytic virus treatment before administration of checkpoint inhibitor. They showed superior responses when combination therapy in which the anti-PD1, anti-CTLA-4, or the oxaliplatin was administered after rather than before the oncolytic virus.
A phase 1b human trial evaluated the safety of the GM-CSF-expressing herpes-based oncolytic virus tamimogene laherparepvec (weeks 1, 4, 6, every 2 weeks) combined with systemic pembrolizumab (week 6, every 2 weeks) for treatment of metastatic melanoma. This therapy had a similar safety profile to treatment with the individual agents. It also induced a 50% reduction in 82% of injected lesions, 43% of noninjected nonvisceral lesions, and 33% of noninjected lesions.29 Interestingly, the anti-tumor responses did not correlate with baseline CD8+ infiltration, PD-L1 status, nor interferon signature.29 As determined by IHC of planned biopsies, the oncolytic herpes virus increased the infiltration of CD8+ T cells in patients who responded to the combined therapy.29
Combination therapy comprising the oncolytic New Castle Disease Virus and a concurrently administered murine-specific checkpoint inhibitor induced abscopal effect on the untreated tumor in a mouse model of bladder cancer.30 On days 7, 9, 11, and 13 after MD49 bladder tumor cells were injected into the flanks of C57BL/6J mice, the right flank tumors were treated with NDV (107 pfu) and the animals concurrently received systemically (intraperitoneally) the anti-PD-L1 or anti-CTLA-4 antibodies. The MTVs of the untreated tumors were reduced, indicative of an abscopal effect.30 These studies show that information from animal studies may be predictive of responses in patients.
Our in-vivo study has several limitations. Since each individual NOG mouse is engrafted with mesenchymal and hematopoietic stem cells from a single human umbilical cord blood donor not shared with other mice, the multiple donors for the hu-NOG mice are likely to have provided a more heterogeneous immune responses than inbred mouse strains (allogenic humanization). We expect that the HLA haplotypes of at least some donors were distinct from the A2058, melanoma tumor line. More complete human immune system with human leukocyte antigen-restricted T cells could be acquired and tested by autologous patient specific transplant of peripheral blood mononuclear cells (PBMCs) and tumor cells and so provided HLA-matched tumor cells. This would likely generate a closer representative of patients’ antitumor response. However, the strength of our study using allogenic humanization is the ability to generate multiple hematopoietic lineages including T and B cells, dendritic cells and NK cells. This in turn means comparable tumor inoculums, comparable duration of tumor engraftment for both the treated and the untreated tumors, and the use of a wildtype human melanoma cell line rather than a cell line with optimized sensitivity to oncolysis.
In conclusion, the data, from this study further support the development of ONCOS-102 and combination therapy of ONCOS-102 with checkpoint inhibitors such as pembrolizumab for the treatment of malignant cancer diseases.
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Måtte legge det ut på denne måten da det er en read-only fil.
Fint om dere ikke deler den så altfor mye 
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Takker. Var en pen inngang det ja 
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Inkluderer dette torsdag/fredagens handel?
Nei. Pr close onsdag forrige uke.
Da ryker de ut nå kanskje. 
For si som Stuffers skriver på Twitter: let the rally begin!
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Tja, jeg tror Citi både kjøper og selger. Det vi ser er nto endring og virker litt for kontrollert. Synes jeg. Om vi ser på kursutvikling og bevegelser på topp50 så er det egentlig marginale endringer. Lite tegn på store endringer i distribusjon av aksjer. Som vi kan se.
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Hun skriver vel ikke det om Targovax ?
Neinei, Nektar Therapeutics. Synes bare den komentaren var litt artig. Trodde det var bare på HO de skrev slikt😅