Replies to post #161177 on NorthWest Biotherapeutics Inc (NWBO)

[TiltMyBrain]

Nothing like hitting a home run with some tail

[longfellow95]

Agree, the tail is the thing, and the fatter and longer the tail the better.

Problem with the CI's is that their tail is not very fat and not usually very long. Hence LP's statement about 25% of 25%.

This linked article describes response to CI's as usually 'binary.'

You either respond well, or you don't respond at all, because of innate resistance. But of the responders, good duration of response is restricted to a proportion, because of acquired resistance. In Melanoma, response rate is very respectable, and duration of response good for most responders (Jimmy Carter?) But it's not the case for most indications.

They use the term ICI's (Immune Checkpoint Inhibitors.)

While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI. However, initial response appears to be a binary event, with most non-responders to single-agent ICI therapy progressing at a rate consistent with the natural history of disease. In addition, late relapses are now emerging with longer follow-up of clinical trial populations, suggesting the emergence of acquired resistance. As robust biomarkers to predict clinical response and/or resistance remain elusive, the mechanisms underlying innate (primary) and acquired (secondary) resistance are largely inferred from pre-clinical studies and correlative clinical data. Improved understanding of molecular and immunologic mechanisms of ICI response (and resistance) may not only identify novel predictive and/or prognostic biomarkers, but also ultimately guide optimal combination/sequencing of ICI therapy in the clinic.

From:-

''Mechanisms of resistance to immune checkpoint inhibitors.''

https://www.nature.com/articles/bjc2017434



Interesting read.

Other statements:-

Failure of ICI therapy can result from defects in any of the steps mentioned above, which can be thought of in three simple categories: (1) insufficient generation of anti-tumour T cells, (2) inadequate function of tumour-specific T cells (Marincola et al, 2000; Bronte et al, 2005), or (3) impaired formation of T-cell memory (O'Donnell et al, 2017; Sharma et al, 2017) (Figure 1).

And a nice statement in their summary:-

Cancer vaccines (Ott et al, 2017; Sahin et al, 2017) are showing promise as a means of personalising cancer immunotherapy and potentially enhancing immune memory. Additional research efforts are underway to identify biomarkers associated with resistance and response to ICI, in parallel with early phase clinical testing of novel immune modulatory agents and novel combinations of immune modulators and ICI with other cancer therapies (Mahoney et al, 2015).

I can't help thinking that these ICI's have more to gain from a DCVax combo than DCVax has!