Dear Stephen, dear all!
1) What do you think about GLIOVAC(https://www.erc-immunotherapy.com/products/gliovac-erc1671)?
And about DCVax?
What is the difference between them?
And there is also dendritic cell vaccine in IOZK (the cheapest one).
Which one has better statistics? Is it worse trying?
1) What do you think about GLIOVAC(https://www.erc-immunotherapy.com/products/gliovac-erc1671)?
And about DCVax?
What is the difference between them?
And there is also dendritic cell vaccine in IOZK (the cheapest one).
Which one has better statistics? Is it worse trying?
2) What about CUSP9v3 protocol effectiveness? Want to try it for my mom. A lot of discussions here in the blog, but can't find information about latest clinical trials results.
3) What do you think about Toca 511? Any experience?
Thank you!
Gliovac is a vaccine that consists of lysate of autologous tumor cells combined with lysate of 3 allogeneic cell lines from a library that match in part with the autologous lysate. The vaccine is injected in combination with GM-CSF as adjuvant.
ReplyDeleteDCVax is an autologous dendritic cell loaded with lysate of the autologous tumor cells. Injection is in combination with Aldara creme because the maturation status of the DCVax itself seemed not optimal.
Dendritic cell vaccine at IOZK (IO-VAC) is a fully matured dendritic cell vaccine loaded with autologous tumor antigens (derived from lysate of autologous tumor cells, or derived from the serum after treatment of the patient with Newcastle Disease Virus and modulated electrohyperthermia thereby inducing immunogenic cell death in residual tumor in the body and thereby releasing antigenic extracellular microvesicles in the serum that contain the tumor antigens).
There are no statistical comparisons between the three approaches.
CUSP9v3 is, at least in my opinion, influencing the surrounding of the tumor but not directly acting as antitumoral strategy. CUSP9v3 drugs can be combined with vaccine strategies.
And one more question, who nows about SurWaxM?
ReplyDeleteHi Irina
ReplyDeleteThe DCs (GlioVax, SurVaxM and DCVax) you mention seems to be the most promising after several trial fails aganist GBM this year.
Unfortunately Tocagen released a discouraging press release just today: http://ir.tocagen.com/news-releases/news-release-details/tocagen-reports-results-toca-5-phase-3-trial-recurrent-brain - so that is probably not the one to pursue right now...
Hi! Thank you so much!
DeleteGliovac/ERC1671 is a vaccine made from whole irradiated tumor cells and tumor cell lysate both from the same patient being treated (autologous) as well as three donor patients (allogeneic). They also prime the immune response with doses of cyclophosphamide and GM-CSF.
ReplyDeleteDCVax is made by co-culturing autologous (from the the patient being treated) dendritic cells, with autologous tumor lysate.
The differences are that:
DCVax is a dendritic cell vaccine, while ERC1671 is not
DCVax only uses autologous tumor lysate, while ERC1671 uses both autologous and allogeneic lysate
DCVax uses only lysate (co-cultured with dendritic cells), while ERC1671 uses both lysate as well as whole irradiated tumor cells.
There have been encouraging results published in phase 2 for ERC1671, but these results were based on a very small number of patients (only 4 treated with ERC1671 + Avastin and 4 treated with Avastin + placebo). This is a smaller number of patients than most phase 1 trials.
Phase 1 results of DCVax were also very encouraging. The full unblinded results of the phase 3 DCVax trial have yet to be published.
It's difficult to compare statistics between two different trials, especially trials with so few patients involved, so its too early to say which method has better statistics. Also trials with DCVax have generally required patients have a complete or near complete tumor resection before treatment, while ERC1671 trials don't seem to require that, so any comparison between the methods wouldn't be exactly fair because of this and other differences.
IOZK does offer an autologous tumor lysate dendritic cell vaccine, and they additionally prime the immune response with Newcastle Disease Virus and hyperthermia. I wouldn't say IOZK is cheaper than DCVax though. Price quotes I've seen for IOZK are only for the first two vaccinations, while price quotes I've seen for DCVax are for the full round of treatments over several years. My impression is that they are equally expensive (at least in the same ballpark), but you pay more the more treatments received. But apart from a special program in the UK with a long waiting list, I'm not aware of any way to get DCVax outside of clinical trials.
Most recent CUSP9 results I've seen are here:
https://academic.oup.com/neuro-oncology/article-abstract/20/suppl_6/vi21/5154229
Again this is a small proof-of-concept trial with only 10 patients reported, so not large enough to draw definite conclusions as to efficacy.
Yes as mentioned in the comment above Tocagen reported unencouraging results about the Toca 5 trial recently. What was actually reported was that Toca511 + TocaFC was not superior to standard treatments (HR=1.06, p=0.6154). The difference between survival in the two arms was not statistically significant, but the standard treatment arm had a slightly long median survival.
What I don't quite understand is why a novel treatment has to display superiority to standard treatment. If the standard treatment is any good, and the novel treatment has equal efficacy, then why not approve it and have more tools available in the toolkit. It's likely that standard treatments work better than Toca511+FC for one set of patients, and Toca511+FC probably works better than standard treatments for another set of patients. Rather than rejecting a therapy based on non-superiority, they should be approving therapies that show at least equivalent efficacy and identifying which subgroups are more likely to respond to each treatment. Responses to Toca511+FC for example seems to be enriched in the IDH-mutant subgroup.
SurVaxM is unlike Gliovac or DCVax, in that it does not use tumor lysate or whole tumor cells, but is a peptide targeted to survivin, a tumor-associated antigen. My confidence in single-targeted immunotherapies is not as much as for multi-targeted therapies, on principle, although SurVaxM has shown some moderately encouraging results in phase 2 in terms of progression-free survival (OS not yet reached).
Thank you so much for such a detailed response!
Delete