Hi
@DTshares
That is 100% correct! You are raising an incredibly important feature of the whole B-cell platform!!!
It doesn't get much coverage here on Hot Copper because we are all so focussed (understandably!) on Imugene's prospects of slowing or even curing active cancer.
However, a huge potential advantage of Imugene's B-cell vaccine approach is that it can be durable over time and produce an immune memory.
And that is
HUGE. Why? Because current manufactured antibody treatments (MABS) have to be continuously re-dosed. They don't hang around and the patient cannot produce them naturally. This makes MAB treatments
waaaay expensive. It also means that any return of the cancer won't be recognised or dealt with until the patient feels unwell again, realises there is a problem, gets to a Dr, has scans done, and is finally re-dosed. By then it could be too late!
By contrast, Imugene's B-cell vaccines teach the immune system to produce its own natural antibodies. Those antibodies hang around, and the B-cells "remember" how to produce them. So if the cancer comes back - the immune system already knows how to recognise the problem and produce effective antibodies to destroy it. Potentially, the cancer could return and be destroyed again without the patient ever knowing!
Which is why Her-vaxx, B-vaxx and PD1-vaxx are described as "vaccines." They don't just treat the disease - they help build immunity against the disease returning.
Waaaaay back in April 2016 the Imugene Newsletter included an absolutely banging explanation - which I think is still the best one they have ever given. Here is the text - it is incredibly well worth a read for anyone who wants to know why Her-vaxx (and the other B-cell vaccines) are so unique and represent a massive leap forward over T-cell MABS:
"The difference between anti-cancer monoclonal antibodies and the current generation of cancer immunotherapies is that the monoclonals represent passive immunotherapy from one small part of the immune system whereas checkpoint inhibitors and other products under development represent active immunotherapy that seeks to prompt the patient’s own immune system to respond with its considerably more diverse repertoire.
Which brings us to what Imugene is seeking to do with its B Cell peptide vaccines. Traditionally vaccines have been used prophylactically, as in influenza or tuberculosis vaccines. They are administered in order to protect the vaccinated subject against disease. Such vaccines often work through the generation of a B Cell response to antigens from the microbe being vaccinated against, so that when the body encounters the real thing it has antibodies that can prevent disease. These protective antibodies are ‘polyclonal antibodies’ in the sense that B Cells from the response can help bind the relevant target in different ways by producing multiple ‘clones’ of target- engaging antibodies.
Imugene is seeking with its B Cell peptide vaccines to create similar kind of vaccines, but for the treatment of disease rather than for prevention. We identify epitopes on known, therapeutically relevant targets where those epitopes generate a B Cell response by the immune system – that is, create antibodies rather than T Cells. We create an antibody-producing vaccine by joining together several of these epitopes in a long peptide, that is, a string of amino acids like one would find in any protein. And we then formulate our vaccine with other known immune-boosting substances that prompt T Helper Cells to boost the polyclonal antibody response.
Our clinical stage B Cell Peptide vaccine, HER-Vaxx, illustrates Imugene’s approach. The target of the vaccine, HER2, was already known from the monoclonal antibody drug Herceptin to be therapeutically relevant in a number of cancers including breast cancer. We originally identified three B Cell epitopes from HER2 that generated a strong anti-HER2 polyclonal antibody response. After some work we created a vaccine in which all three epitopes came together in a single peptide, and that peptide was combined with CRM197, a so-called ‘carrier protein’ that provides an immunogenic kick for the Prevnar vaccine which is routinely given to prevent pneumococcal infections.
More recently we’ve experimented in our vaccine formulation with adjuvants, which are other substances known to turn up an immune response. What we’ve looked for in the animal models aswe’ve gone along is increasing numbers of antibodies targeting HER2, and as our Chairman noted above we now have vaccines at least twenty times as powerful as those we started with.
One significant reason why we think this approach has merit, with the potential to lead to great outcomes for cancer patients as well as significant creation of shareholder value, is because we think we can go one better than the monoclonal antibodies, in terms of killing cancer cells.
Peptides are inexpensive to manufacture compared to monoclonal antibodies. More importantly, with our vaccines we can go after more than one B Cell epitope at a time with multiple different types of antibodies, giving us the opportunity to hit cancer cells harder than a monoclonal could. The commercial potential of all this is suggested by the high sales for leading monoclonals – Herceptin peaked at US$6.85bn in net sales for Roche in 2014.
Another reason why we believe our approach has merit has to do with an advantage of B Cells over T Cells. In their attempts to generate a T Cell response, cancer vaccine developers often face a problem called ‘MHC restriction’. Put very simply, MHC restriction means that each person’s Cytotoxic T Cell response is genetically determined (Australia’s Peter Doherty figured this out in the early 1970s and won the Nobel Prize for Medicine in 1996 for his efforts).
Consequently, many patients won’t respond to certain types of T Cell epitopes, limiting the vaccine to a certain class of patients. B Cell epitopes don’t have this problem andtherefore our kind of vaccine is universal. B Cell peptide vaccines don’t have an MHC restriction problem.
Finally, we think our B Cell vaccines have an advantage in the issue of immune ‘memory.’ With many prophylactic vaccines, you only need to get them once because the antibodies continue to circulate for decades afterwards. We believe our vaccines, being oriented towards antibody production, have a similar memory effect. Consequently, there is potential our vaccine could help many patients remain in remission for a long time after their initial treatment." Source: https://static1.squarespace.com/sta...49046297/2016 04 13 Newsletter Edition 01.pdf
Seriously - (and not meaning to channel our
pathetic clown of a PM) - how good is that???!!!!!!!!!!!!!!!
Cheers
Dave
(20min delay)