At last month’s Congress we were lucky to meet Dr Andrew Allen, CEO and Co-Founder of Gritstone bio, for a conversation about cancer vaccines and immunotherapy targets. He joined us at the event for the Cancer and Immunotherapy Vaccines track, and we were glad to sit down with him for more insights into his work and the work of the field. We hope you enjoy the interview!
As Dr Allen mentions, he is the CEO and Co-Founder of Gritstone bio, a publicly-traded company based in the US. Their facilities are on both the East and West Coasts. Gritstone describes a commitment to “progressing the field of immunotherapy”, which meant that Dr Allen was in a good position to chair the track!
One of Dr Allen’s sessions was on neoantigen immunotherapy for solid tumours, so we asked him to share a bit about what this involves. He suggests that this is an “idea that has been around for about 7 or 8 years”. Data published in 2014 indicated that “mutations in genes created altered proteins that could function as antigens for the immune system”. Thus, the neoantigen.
“The achilles heel of cancer seems to be that when those proteins change they can provide targets for the immune system.”
For Dr Allen, there is then an “arms race” between “a cell that’s trying to turn into a tumour cell, proliferating without restraint”, and the host’s adaptive immune response, “trying to identify foreignness, and eliminate it”.
“We’re trying to essentially tilt the battlefield in our favour by driving strong immune responses against those tumour neoantigens.”
Luckily, some pretty “elegant biology” works with us here. The mutations are only found in the tumour and are “foreign to your immune system”. Although this sometimes happens naturally, without attracting attention, T cells can “often” enter the tumour but “something stops them from completely eliminating the tumour”. However, most solid tumours don’t have lots of pre-existing T cells. Therefore, we need to “take a step back” and “generate the T cells”.
“We use vaccines to generate those T cells.”
Vaccines on the scene
Dr Allen mentions that vaccines are used to generate T cells. We asked what a successful cancer vaccine might look like, or what the ultimate goal for vaccine developers might be. For solid tumours, the “goal is to prolong survival”. Explaining the role of “biomarkers” or “surrogate markers”, Dr Allen suggests that the “goal” is to “impact those biomarkers in a very striking fashion”. This often happens in patients with advanced disease, before the platform can be moved backwards into an “earlier stage population”. In this population, the immune response is “better” and the tumour presence lesser, so there is greater opportunity to make a demonstrable difference.
The question of clinical trials
Some of the conversations that took place at the Congress were centred on the issue of improving clinical trials to produce better outcomes. We asked Dr Allen what his views on this issue are. For him, it’s a “really interesting area”. He suggests that in oncology, “we’ve been using the same endpoints for about 20 years now”.
“You’re looking for lesions to get smaller, and if they don’t get smaller, you say ‘that therapy doesn’t work’.”
However, this isn’t appropriate for immunotherapy, in which the goal is T cell proliferation within the lesions. When the T cells enter lesions, they can often get bigger, misinterpreted as “progression of disease – that’s failure”. What might actually be happening is proliferation of T cells causing a temporary enlargement, before the T cells “go to work” and the tumour shrinks. “Pseudo-progession”, says Dr Allen, is a “recognised problem” particularly for melanoma.
With vaccines, for cold tumours, the tumour has no T cell population until vaccination, where the notion of lesion expansion is once again “important”. Additionally, there is “good evidence” that some tumours that are responding to therapy develop mini lymph nodes! Lymph nodes are “fixed structures that are stable over time; they occupy space”.
“The expectation that the tumour has to go away for there to be a good outcome I think is based on these flawed ideas from the past.”
With these concerns in mind, Dr Allen suggests that radiology is “struggling” to “meet our needs of being a predictive biomarker”. His question, then, is “do we have something better”, to which he believes we can answer positively! The answer is “circulating tumour DNA”, which can be measured in the blood.
“You treat a patient and if their CTDNA goes down, they are likely to do well.”
This is a well-established approach, but the field has not yet made the transition.
“I think we’re going to find that CTDNA actually is a much better surrogate for overall survival, with immunotherapy.”
What was happening at the Congress?
We asked Dr Allen about his interests at the event, and he shared what he was most looking forward to. Apart from presentations from BioNTech and Moderna, Gritstone’s “competitors in the space”, there were opportunities to meet with other players in the field.
“It’s going to be an exciting year and I’m looking forward to just chatting about that with all of the experts here at this conference.”
We are grateful to Dr Allen for his time and his useful insights into technical details and wider field ambitions. We look forward to more from Gritstone bio at future events! For more interviews with experts in the cancer space, click here to subscribe. To see a breakdown of the event, click here for the post-event report.