| aekusterer | Sunday, 12/18/16 07:24:03 PM | | Re: None | | | Post # of 90480 | | |
Statistics that support Dendritic Cell therapy:
1) In 21 dendritic cell studies world-wide, lives have been extended 65-230 weeks vs. 58 weeks for control average.
2) One patient is alive at 14 years, and several others are long term since DCVax began in 1998.
3) LL estimates that 25-30% of DCVax patients will survive > 5 yrs, and those will have detectable favorable early parameters.
Main Trial: 83/221 = 38% of 221 treated patients have not progressed. These are probably in mesenchymal subclass. Before being randomized into 221 treatment and 110 placebo, all early progressors were moved out of main trial at baseline MRI into:
Information Arm (2008-12): with 20 rapid progressors and 25 pseudo progressors. 10/25 = 40% of pseudo progressors are alive at > 4 yrs. These are probably mesenchymal.
Pseudo Progressor Arm (2012-13): 22 patients. No discussion by LL; may need more time.
Favorable early survival parameters by LL:
1) "All long-term survivors are in the mesenchymal subgroup", because virulent mutations give more immune system targets.
2) The presence of TILs (tumor infiltrating lysates like CD-8 killer T-cells) in the tumor micro-environment, particularly before DCVax, indicates an initially stronger immune system.
3) A strong overlap between the receptors in the tumor and in the blood is good, and indicates an early systemic response by the immune system. This, and increased TILs, can also be correlated with later DCVax injections.
4) A reduced presence of TGF-b in the tumor micro-environment indicates less suppression of the immune system response. This is similar to less PD-L1. More PD-L1 in the tumor response to DCVax can be treated with a CI, but CIs need DCVax to mobilize TILs to be effective.
Notes:
1) The use of many (100,000+) diverse patient antigens derived from DCVax autologous lysate is safe, and is proving superior to many attempts using a few selected antigens due to the heterogenous nature of GBM.
2) Long survival tails indicate that immune system memory is working, a key need for recurring GBM. These tails set immunotherapy trial evaluation apart from standard trial MOS (median overall survival) evaluation.
Conclusions:
1) DCVax is showing efficacy.
2) DCVax is safe.
3) Immunotherapy trial endpoints need revision.
4) The mesenchymal group is important.
siliconinvestor.com |
