Replies to post #207496 on NorthWest Biotherapeutics Inc (NWBO)

[iwasadiver]

Of course it's an open question. However, Jondoe thinks he's somehow refuting everything with links to other unproven technology. So what's his point? What's your point?

[Extremist223]

I think adaptive resistance and anergy is a much bigger concern. Why would de novo t cells track to the tumor if it wasnt the case?

Also the end of Dr. Prins video presentation highlights all about mutational burden, neoantigens arising from them, t cell receptor sequencing etc.

[CogDiss 1188X]

Hi jammy, here’s some early evidence (2004) that whole tumor lysate primes DCs to generate tumor antigen specific T-cells in humans:

Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma.
https://www.ncbi.nlm.nih.gov/m/pubmed/15256471/
The antigens tested for in the study aren’t neoantigen, but are instead known tumor associated antigens. Is the assertion that DCs can’t identify neoantigens? Very unlikely since that’s its job, correct?


As you’ve suggested, DC vaccines could work through other mechanisms as well.
For instance, they also decreased Treg cell populations and decreased expression of CTLA-4 on peripheral blood T cells, after DC vaccination, which was correlated with longer survival in the phase 1 trial with glioblastoma patients (Liau and Prins). For those not up on the immune system components, DC Vax released two brakes on the immune system. And unlike ICIs, we get a two-for-one, without the added toxicity and potential of hyper-progression.

Monitoring of Regulatory T Cell Frequencies and Expression of CTLA-4 on T Cells, before and after DC Vaccination, Can Predict Survival in GBM Patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317661/#!po=0.724638



Liau and Prins milked that trial for some more data on mechanisms of efficacy—this time showing that DC vaccination increased the sensitivity of T-cells to cytokines in a way that increased clinical efficacy.

Cytokine responsiveness of CD8+ T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039989/

These are the kinds of effects that we would expect to see by recruiting the key component of the immune system in the treatment of cancer exposing it to the whole tumor lysate under the right conditions (which I know you know — just commenting for the skeptics ;-) )