RE:RE:RE:RE:RE:RE:RE:RE:RE:CD8+ TiLs and T-cell exhaustionOctober 14, 2024 - Transgene’s therapeutic oncolytic virus / vaccine candidate TG4001when combined with the activated/native Fc checkpoint inhibitor Bavencio (avelumab) failed in their Phase 2 clinical trial recurrent or metastatic HPV16-positive cervical and anogenital cancers - in much the same way that ONCY's pelareorep did in their Phase 2 Bracelet-1 study.
Transgene's clinical trial assessed the effect of adding TG4001 to the checkpoint inhibitor Bavencio. TG4001 is a viral-based vaccine that expresses HPV16 E6/E7 proteins and IL-2.
The failure happened for the same reasons - the CPI Bavenio has an activated/native Fc region attached to the CPI as outline in the below referenced post.
https://www.fiercebiotech.com/biotech/transgenes-viral-cancer-vaccine-flunks-midphase-test-subgroup-signal-spurs-ongoing-analysis Noteable - (10/4/2024 7:21:30 PM)
RE:RE:RE:RE:RE:RE:RE:RE:CD8+ TiLs and T-cell exhaustion
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we know that the PD-1 checkpoint inhibitor avelumab is unlike other CPIs given its active Fc region. ONCY's CMO Thomas Heineman has made this known in multiple presentations he has given.
" Unlike other approved anti-PD-L1 antibodies, avelumab has a native Fc region that retains FcγR binding capability."
Avelumab is cleared faster and has a shorter half-life than other anti-PD-L1 antibodies, such as atezolizumab and durvalumab, which appears to negatively impact T cell clones expansion. Consequently the addition of the PD-L1 inhibitor avelumab, unlike atezolizumab, eliminated pre-existing TIL expansion in the blood and reduced pelareorep's clinical activity, and has repeatedly proven its ineffectiveness in other clinical trials with other I/O agents besides pelareorep.
https://stockhouse.com/news/press-releases/2024/05/24/oncolytics-biotech-xae-asco-abstracts-highlight-pelareorep-s-potential-in
Noteable - (10/4/2024 7:21:30 PM)
RE:RE:RE:RE:RE:RE:RE:RE:CD8+ TiLs and T-cell exhaustion
It's remarkable how those like Quentin30, who doesn't own any shares on ONCY, keep trying to post unfactual information about Bracelet-1 when we know that the PD-1 checkpoint inhibitor avelumab is unlike other CPIs given its active Fc region. ONCY's CMO Thomas Heineman has made this known in multiple presentations he has given.
" Unlike other approved anti-PD-L1 antibodies, avelumab has a native Fc region that retains FcγR binding capability."
Avelumab is cleared faster and has a shorter half-life than other anti-PD-L1 antibodies, such as atezolizumab and durvalumab, which appears to negatively impact T cell clones expansion. Consequently the addition of the PD-L1 inhibitor avelumab, unlike atezolizumab, eliminated pre-existing TIL expansion in the blood and reduced pelareorep's clinical activity, and has repeatedly proven its ineffectiveness in other clinical trials with other I/O agents besides pelareorep.
https://stockhouse.com/news/press-releases/2024/05/24/oncolytics-biotech-xae-asco-abstracts-highlight-pelareorep-s-potential-in