Oncolytics Biotech Inc T.ONC

CAR-T Abstract from Mayo Clinic (Vile group) using pela

[westcoast1000]

Here are the final two sections:

Results:By using OV in combination with EGFRvIII CAR T cells, we were able to generate a CD8 CAR population with TCR specificity for both the EGFRvIII and OV epitopes. These dual-specific (DS) CAR T expressed a memory phenotype and persisted for much longer than conventional CAR T cells. Further, we showed that these DS CAR T cells are more cytotoxic and can respond more rapidly than their conventional counterparts. We created a novel delivery mechanism for this combination OV + CAR T therapy using virus-loaded CAR T cells to bypass initial antiviral clearance from the immune system. Treatment with these OV-loaded CAR T cells lead to significant benefit in mice with HGG tumors which could be further enhanced by a systemic boost with OV, which rapidly re-activated DS CAR T cells against tumor and resulted in long-term cures of greater than 80% of treated animals.Conclusions:These promising results show that DS CAR T cells can overcome the critical therapeutic challenge of CAR T as a treatment for solid tumors. Given these promising results, we will go on to develop a clinical trial in which CAR T cells will be pre-loaded with OV and administered intravenously to patients with HGG, followed by systemic boosting with virus to re-activate DS CAR T cells against their tumor.

[westcoast1000]

The CAR-T results refer to murine model patients (mice) with high grade glioma (seriously bad brain tumor). 

[Noteable]

Two major take-aways: 1) "These dual-specific (DS) CAR T expressed a memory phenotype and persisted for much longer than conventional CAR T cells". [Conventional CAR-T cells typically experience T cell exhaustion with loss of T-cell persistence and loss of effectiveness resulting from the immunosuppressive TME which ONCY's pelareorep is able to overcome by remodelling the TME for

[Noteable]

" Unfortunately, the efficacy of CAR T cell therapies against solid tumors is significantly limited, in large part due to impaired expansion/persistence in the immune suppressive tumor microenvironment (TME). " [ONCY's pelareorep is capable of overcoming an immune suppressed TME to facilitate the addition of various I/O agents, as decribed in my earlier post ] https://meetings

[Noteable]

Coffey mentioned in ONCY's last investor call that ONCY was already using(?)/planning(?) pelareorep in a clinical setting with an un-named BP's CAR-T construct 

[Eileen68]

Correct and in addition the unnamed BP had successfully replicated the results once and is currently working on a second confirmatory experiment. (Specifically to ensure no mistakes were made the first time)

[Noteable]

Replicating the positive results first seen with the CAR-T construct pre-loaded with pelareorep is a "Good Thing".

[jimsenior]

@Noteable. Yes a Good Thing; 100 per cent. I am just curious about a few things. The first abstract was for brain and melanoma. The second abstract was for HGG. The CAR T cells used in the current abstract were EGFRvIII, and I am guessing that is a different CAR T than that used in the first abstract. Just wanted to confirm that. Second, it appears they did not use a boost in the current

[Noteable]

This is the abract that I have been commenting on...  https://meetings.asco.org/abstracts-presentations/222671

[Noteable]

* abstract *

[Noteable]

"OVs and CAR T cells were given systemically by tail vein." Given systemically by 'tail vein" means live mice.

[jimsenior]

Does this current abstract differ in that they used EGFRvIII CAR T cells? And is it correct they did not use a boost in the current abstract? Any guesses as to the pharma.  BMS? Roche? They have so much on the go. Will they tie it a bow? Many answers needed.

[Noteable]

jimsenior - the abstract demonstrated the benefit of a dual-specific (DS) CAR-T that was comprised of an OV (reovirus) and EGFRvIII CAR-T cells which was a novel and effective delivery system that was further enhanced by a systemic boost with reovirus which when given alone for a second time, the "boost" rapidly reactived (DS) CAR-T cells against tumors and resulted in long-term

[jimsenior]

@Noteable. We are both talking about the CAR T  abstract  at ASCO 2023. I am reasonably confident they did not actually  boost with OV. The eighty per cent figure comes from the first abstract, They are saying IF they had boosted they expect the same results, 80%, which were achieved previously. This too is a GOOD THING. I trust you see that I am trying for clarity. BEST

[Noteable]

This is all I have to go by ....  so I don't really know and thus will leave it to someone else to interpret. "Treatment with these OV-loaded CAR T cells lead to significant benefit in mice with HGG tumors which could be further enhanced by a systemic boost with OV, which rapidly re-activated DS CAR T cells against tumor and resulted in long-term cures of greater than 80% of treated

[jimsenior]

@Noteable. An excellent solution. I shall resist trying to tilt the answer in my favour. It is not clear. After all, the goal is not to be right, but to get answers for those brave youngsters.

[Noteable]

I agree with you that the abstract implied the"If" a booster was used  ... and maybe that will be clarified going forward.

[Capitalista]

The text in the abstract is confusing - they use future tense (". . .could be further enhanced by a systemic boost with OV") and past tense (. . .which rapidly re-activated DS CAR T cells against tumor and resulted in long-term cures of greater than 80% of treated animals").  Perhaps they need a better copywriter.   In the previous murine experiment, only one "

[askretka]

Sign up for the KOL webcast on Monday.  There's even a spot to ask a question. I have a strong feeling they aren't going to be able to answer all the questions everyone has. Looking forward to what Dr. Vile has to say. It's been about two years since the CAR-T KOL after the 7/7 mouse cures. I've been following Cantor Fitzgerald 's coverage pretty closely and even sat in

[jimsenior]

Good Morning Capitalista, I refer you to a press release dated April 14, 2022. In that release, it is stated  -  tumor cures greater than 80% of treated mice in each model. So, it does seem that no OV boost in this current trial. Yet it seems they feel, had we boosted we expect that we would have attained 80% cures. If that is correct, it speaks to me of a high level of confidence and

[Capitalista]

Thanks, jimsenior - I'm happy to say I'm the one who stands corrected.  80% cure is better than only one cure.  I went back in the NRs and found I was mixing up the  Goblet PDAC resusts (where one "complete response" was reported) with the pre-clinical CAR-T/Pela research.  Memory has never been my strong suit.  

[westcoast1000]

Folks, you may be discussing cures in mice cancer cells, not in live mice.

[Buckhenry]

I am just elated they are trying to cure all the mice. Hopefully I will see more of them in my house in the future. If they could do that with people this company might be worth at least.... 10b?????  Just a pure guess on my part!!

[Azzak34]

Uh oh, someone doesn't understand clinical trials! 

[Buckhenry]

I think we should save the mice and use the dreamers for research instead. But I guess even the researchers have minimum  standards!!!

[Azzak34]

They did save the mice idiot, go back and read! 

[jimsenior]

Hello Henry, Let me introduce you to James P. Allison, 2018 Nobel Prize Winner for Physiology or Medicine. The first for cancer in 28 years. He is best known for elucidating the mechanism behind T Cells activation, and pioneering the first immune checkpoint inhibitor. Yervoy. I cannot remember his exact words, but he asserted that animal models were essential to his work. I believe Allison

[Buckhenry]

You folks are so high strung  you don't know how to laugh a little...  a wise man said ... laughter is the best medicine.  Lighten up or you may need some blood pressure  medication. 

[Azzak34]

Laughter don't cure stupid you zilch. Your banter is awful by the way. How old are you? 

[Buckhenry]

I think assak may need that blood pressure  medication or a shrink and I will type slower so he can possibly comprehend some of it. Laugh a little folks and lighten up. Nothing said on here will affect the outcome anyway. Blue skies ghurls. 

[Azzak34]

I would suggest learning how punctuation works. That regulates the speed at which people read..... sentences. 

[askretka]

https://m.facebook.com/story.php/?story_fbid=696466984055078&id=118033555890 ---------------------------------------------------------------- A video on Dr. Vile from Mayo clinic. He's definitely a huge asset to our Science Advisory Board. Cheers!!!

[Lesalpes29]

Thank you  askretka for the work you do here. Tomorrow is the Day and I wish best of luck to every long. Have a good day. 

[Noteable]

Link posted by Dude on STwits. Take particular note to the reference on CAR-T and an immunosuppressive TME, which I addressed in an earlier post on this thread. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115105/

[askretka]

Subgroup 2: RAS/MAPK pathway mutations Cerebral hemispheres Subgroup 3: RAS/MAPK pathway mutations Thalamus, brainstem, spinal cord I thought the fact two of the 3 subgroups have RAS in them could be potentially significant as well. Cheers!!!!!!!!!!!!!!!!