With just weeks to go until the World Vaccine Congress in Washington this April, we are delighted to share another in our series of exclusive interviews with some of the fantastic speakers lined up for the event. This interview was a zoom conversation with Dr Niranjan Sardesai, founder, President, and CEO of Geneos Therapeutics. Our conversation explored the work that Dr Sardesai and his team and doing in developing personalised cancer vaccines, and how this interacts with research happening in the infectious disease area. A full transcript can be found at the bottom of the page. We hope you enjoy it!
Geneos at a glance
Our first question aims to provide a bit of context to Dr Sardesai’s work and his presence at the Congress. He describes Geneos as a “clinical stage immuno-oncology company” that is developing “exquisitely personalised cancer vaccines” based on its GT-Epic platform and importantly, one that is already seeing dramatic tumour reductions in clinical trials.
How does Geneos approach cancer vaccines?
Dr Sardesai uses the term “exquisitely personalised” in his previous answer, and we were curious about how Geneos is pursuing this goal. For Dr Sardesai, “these are really exciting times for the cancer vaccines field”. Although the understanding of the immune system’s response to tumours is “not a new finding”, the challenge has “always been” encouraging this in more patients.
The approach that Geneos is taking is a “holistic view”. The team wanted to identify the tumour-specific antigens, to develop the right immunity to those antigens, and to understand the “ideal clinical settings”. Thus, the concept of the personalised vaccine, “truly tumour derived from each patient”, was developed. The mutations in tumours are twofold; not only do they enable the cancer to “avoid the immune system”, but they can act as the “Achilles heel of the tumour”, marking the cells to the host immune system.
“So what we’re trying to do is exploit those differences in the cancer cell and because these differences are idiosyncratic, they’re different from each patient to patient. The products that are designed based on these differences necessarily have to be personalised.”
The “core” of the GT-Epic platform is understanding and identifying the unique makeup of each patient’s cancer cell, developing their personalised vaccine, and then treating the patient.
What challenges do these vaccines bring?
From the sounds of it, developing personalised cancer vaccines is not a simple process, so we asked for a bit of a rundown of some of the key challenges that Dr Sardesai and his team encounter. This is a “really fundamental question for the field”, says Dr Sardesai. He suggests that because the technology to identify changes in tumours has been developed through “tremendous improvements in sequencing capabilities”, we are in the “golden age of genomics and bioinformatics”. As such, “external developments” in the wider vaccine space are enabling solutions in the cancer vaccine arena.
“I feel like this is the right time and the right place for cancer vaccines, personalised cancer vaccines, because some of the key technological hurdles around identification have been addressed by the field as a whole. So we’re certainly grateful for that.”
However, for each patient there can be “hundreds of somatic changes”. Consequently, identifying “targetable neoantigens” presents another challenge. Among the community Dr Sardesai identifies “different methods” for identifying these, but for him and his team, the lesson they are taking forward is that “targeting more” of these neoantigens is “going to be preferable”.
“Geneos is taking the approach that we identify all targetable mutations, and we incorporate all of them into our tumour vaccines and let nature make the call.”
Dr Sardesai states that lessons from natural immunity show that the immune system is capable of “driving responses to a large range of immunogens” every day. Thus, the team at Geneos puts the “decision-making process” in the hands of the individual immune system. Another challenge is that “patients and the tumours are certainly not waiting around” for treatments to be developed.
“Speed is of the essence.”
Therefore, a challenge is keeping down the turnaround times from biopsy to treatment. With their DNA-based platform, Dr Sardesai and colleagues have already shrunk this to 6-8 weeks. However, they “know” they can do it in under 4 weeks. This is where a clinical development aspect comes into play, because “sometimes clinical development decisions are made based on the capabilities of the platform”. For example, if a platform has a long turnaround time, it may not be applicable to certain types of cancer or treatment settings.
“What Geneos has done is we’ve shown that we are treating patients with bulky tumours.
So far, results from the field are exciting, showing that personalised cancer vaccines can work in earlier stage cancers to “prevent recurrence.” Perhaps even more dramatic is that Geneos has shown that it can reduce – and even eradicate – bulky tumours and their metastases in patients with advanced cancer. These clinical results have led to the planning of a potentially registrational clinical trial.
Infectious diseases and cancer therapy
For many of our speakers who are not directly engaged in infectious disease research, the field has had implications for their work, whether in terms of COVID-19 disruptions or accelerated technological developments. We asked Dr Sardesai about the interplay between his work and infectious diseases. Interestingly, Dr Sardesai entered the field “from the infectious disease side” and he identifies a “phenomenal impact” on the approach he is taking to cancer vaccines.
A key similarity is the notion of central tolerance. Simply put, years (and years) of evolution have developed an immune system capable of “identifying what is self from foreign”. Although we do experience certain auto-immune diseases, in general, the immune system is fairly confident in making these distinctions. This has been “exploited fundamentally” in infectious disease research, and the cancer field can learn from this by seeing the link between “what is it that drives immunity” and tailoring the immunity to the pathogen.
In cancer, the tumour neoantigens are “non-self”, so Dr Sardesai suggests that “just as we think of viral antigens and bacterial antigens as foreign”, these neoantigens can be perceived as “foreign”. However, for infectious diseases the aim is usually prevention, and in Dr Sardesai’s work the goal is therapy.
As he identifies lessons he has learnt from infectious diseases, Dr Sardesai also hopes to share insights the other way. For example, with recent COVID-19 vaccines, they were “very, very effective” in terms of antibody responses, but “it’s been challenging to do clearance because of lack of T cell immunity”.
“So what we love about the idea is that I think we started out from the infectious disease, we all learnt a lot, what we learnt through developing cancer vaccines is what drives effective cellular immunity, which can then go back into developing better infectious disease vaccines.”
We also like the idea of interaction between the different areas of vaccine development, and this leads us nicely into our final question!
Why the World Vaccine Congress?
We love to understand more from our speakers when it comes to what brings them to the Congress. Dr Sardesai puts it perfectly when he says that it’s been organised to cover “all things vaccines”! This means that “concurrent sessions” will cover every aspect of vaccine development and deployment. In particular, he’s looking forward to the regulatory tracks because “these developments that are going on are happening in real time”.
“I’m looking forward to…being able to interact with colleagues across different silos.”
We really enjoyed this conversation with Dr Sardesai and hope you did too. If you would like to hear more on his work, join us at the World Vaccine Congress this April. To read the full transcript, see below!