Replies to post #41910 on OncoSec Medical Inc (ONCSQ)

[Hargrove]

Sometimes I think "hschlauch" is a "pseudonym" for Dr. Pierce! Anybody ever seen "hschlauch" and "Dr. Pierce" in the same place at the same time? This is something I think about most often when there is a full moon......anybody else having the same thought?

Not sure what we'd do without "hschlauch" and his enlightening posts!?!?

Keep those good vibes flowing!

THANKS!

[dr_lowenstein]

LOL and you know all of that how? hmmmmmmm

[lasers]

For those not familiar with $ONCS's new GENESIS™ delivery EP.

The OncoSec GENESIS™ research generator was developed specifically for gene electro-transfer. It features customizable electroporation parameters for construct-specific optimization of expression, and it is the only in vivo electroporation device enabled with TRACE™ Technology (Tissue-Based, Real-Time Adaptive Control Electroporation.)

TRACE™ technology incorporates an electrochemical tissue-sensing control system to automatically adjust pulse width and treatment duration in real time during the electroporation procedure. This feature enables tissue- and therapeutic-specific delivery optimization, maximizing uptake of the therapeutic while reducing unnecessary cell ablation or damage. In research models, GENESIS™ with TRACE™ has yielded higher and more consistent in vivo protein expression versus fixed-parameter electroporation, even in heterogeneous tissues.

Potential advantages of GENESIS™ with TRACE™ for use in murine models include robust and conformationally-native in vivo expression of difficult proteins, including GPCRs and receptors that function in multimeric form. Moreover, the consistent results obtained with these technologies in heterogeneous tissues support reliable intratumoral delivery of a wide variety of DNA-encodable therapeutics across multiple syngeneic, xenograft, and PDX models. Using these technologies, OncoSec has expressed more than fifty proteins in vivo, including multimers and structurally-complex fusion proteins, and no protein tested to date has failed to successfully express.

The OncoSec Technology Access Program makes OncoSec's electroporation technologies available to collaborators for preclinical research. Devices are available for intratumoral, intradermal, and intramuscular delivery.

[Titan V]

Thanks for your reply hschlauch. Looking forward to additional insights whenever you get the chance.

[hschlauch]

The FIRST multigene construct data not only show successful expression of multiple encoded genes in a single product, but the selected genes highlight a rational approach to increasing intratumoral CTLs. The flt3l-encoded gene fused with an antigen is going to accomplish more than just drive a single tumor antigen-specific immune response.

Flt3l fused with an antigen will lead to endogenous expansion of dendritic cells and maturation of those cells (through activation with the fused antigen). The maturation of dendritic cells through activation with an antigen increases the costimulatory molecules CD80 and CD86. So, not only does the fusion of Flt3l and an antigen lead to dendritic cell expansion and activation, but it vastly increases CD80 and CD86 intratumorally.

And what do we know about CTLA-4 on T regs? They outcompete CD28 binding on T cells for CD80 and CD86 on mature dendritic cells. By significantly increasing the number of CD80 and CD86 costimulatory molecules on dendritic cells, you're shifting the balance of power in favor of T cell activation. You end up with more mature dendritic cells per T reg, thus altering ratios that would otherwise suppress T cell activation and proliferation.

Bottom line: the combination will lead to more intratumoral CTLs. It will accomplish this by improving neoantigen presentation, increasing mature antigen presenting cells intratumorally, and mitigating the overall effect T regs have on immune suppression.

[dangerM]

Oncosec's multigene-construct / FLT3-ligand

just something interesting to note, other news from the AACR2018: someone has posted quite a comprehensive set of slides (all slides?) on a combo of low-dose radiation with an FLT3-ligand.

Just a small sample (n=9, eligibility criteria: 2nd line, stage 3 or 4 NSCLC "not amenable to curative therapy") and a questionable short observation period (endpoint: progression free survival at 4 weeks).

However, IMHO it shows that Flt3 might be an really interesting choice!

Ohry - FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer #AACR18 1/x https://t.co/QhZhrlVNfa pic.twitter.com/d8lAQGj1w4

— Bertrand Delsuc (@BertrandBio) April 15, 2018