Friday, September 21, 2018 3:23:37 PM
I still have to write this together with some more text and send it to the company (who hopefully are not too nerved about these citizen scientist/investor mails), but I think only dosing could be tricky with the new combo. Just as a preview:
See the ESMO 2014 ("Immune correlates of intratumoral IL-12 electroporation") mouse data which shows 20/20 (100%) complete responses of the treated lesions. Of course, it's the same identical (low-immunogenic!) cancer cell line in all these mice, but an approach with 100% perfection: whoa! I think it was key that the lesions could be "finished off" within 7 days (IMHO the honey moon period before a Treg rebound slows down the process).
In contrast, look at the data on the AACR 2017 poster ("Intratumoral delivery P2A-linked Bicistronic IL-12 construct leads to high intratumoral expression and systemic anti-tumor response"). By any means the P2A-linked plasmid is more effective (in terms of more IL-12 produced, IFNg levels). However, look at the most right panel for the tumor volumes (treated flank): the tumor volume of the treated flank does not go back as strong as with the iRES plasmid (whereas the untreated flank does show a much better effect).
I am not sure about the reason what happens in the treated flank. If it was the "Treg rebound-effect" I'd expect it maybe around day 10, but the early curves are already different from the iRES in the middle panel.
As well, the not treated flank in the lower right panel shows much reduced tumor growth already very early (where I wonder if it's already trafficking immune cells or some systemic, bodywide spill-over of the immense amount of IL-12 produced at the treated flank).
So the really, really, really important thing will be to pre-clinically and perhaps/probably also clinically test out the optimal dose levels of a P2A-plasmid.
The P2A is very definitely an improvement, since it gives them more leeway to alter dose levels, but they'll have to test out how to use this additional freedom even in the single-compound version. If I were one of the >5% investors with regular/direct contact to the company, I'd probably ask this in person: What have you done to determine the ideal dose level of the P2A-linked plasmid for IL-12? Is it possible to "overdose" in terms of attaining the most effective dose? After determining this optimal dose, have you also tested different levels of Flt3L?
Have a great weekend everyone!
dM
Recent ONCSQ News
- Form SC 13G/A - Statement of acquisition of beneficial ownership by individuals: [Amend] • Edgar (US Regulatory) • 02/13/2024 07:30:19 PM
VHAI - Vocodia Partners with Leading Political Super PACs to Revolutionize Fundraising Efforts • VHAI • Sep 19, 2024 11:48 AM
Dear Cashmere Group Holding Co. AKA Swifty Global Signs Binding Letter of Intent to be Acquired by Signing Day Sports • DRCR • Sep 19, 2024 10:26 AM
HealthLynked Launches Virtual Urgent Care Through Partnership with Lyric Health. • HLYK • Sep 19, 2024 8:00 AM
Element79 Gold Corp. Appoints Kevin Arias as Advisor to the Board of Directors, Strengthening Strategic Leadership • ELMGF • Sep 18, 2024 10:29 AM
Mawson Finland Limited Further Expands the Known Mineralized Zones at Rajapalot: Palokas step-out drills 7 metres @ 9.1 g/t gold & 706 ppm cobalt • MFL • Sep 17, 2024 9:02 AM
PickleJar Announces Integration With OptCulture to Deliver Holistic Fan Experiences at Venue Point of Sale • PKLE • Sep 17, 2024 8:00 AM