Interview: Analysing the potential for DNA vaccines

DNA Vaccine Potential

Dr. Niranjan Sardesai, Chief Operating Officer, Inovio Pharmaceuticals was kind enough to take the time to speak to us to give his viewpoint on DNA Vaccines, in particular, their potential across a range of cancer indication.

What is the potential for DNA vaccines across a broad range of cancer indications?

It’s a great time to be in the DNA vaccine arena. There’s a good chance we’ll look back at the next 10 years and see them as the decade of DNA vaccines.  Why? Because over the last several years, there have been some key scientific papers and developments in the field that all point towards important breakthroughs in enhancing immune responses and then enhancing both the quality and magnitude of immune responses that DNA-based vaccines have elicited, in a wide variety of model systems as well as in the clinic.

In addition, DNA has long enjoyed a strong safety record in comparison to other viral vaccine approaches. The challenge has been to translate that safety profile into meaningful efficacy profiles to both treat and prevent hard-to-treat diseases, like certain infectious diseases and cancers.

Over the last few years, some of the work that has come out both from our group as well as from other DNA vaccine practitioners that shows we may be close to demonstrating some real tangible efficacies to go with the established strong safety profile.

From a cancer perspective, I think what makes DNA-based vaccines exciting is that we’ve been able to show we can break tolerance in a number of different animal models. In humans, Inovio  and others have now shown that you can generate robust and durable T-cell responses, both CD4 and CD8, or killer T cells. In a paper we published last year in Science Translational Medicine, we were the first group to show that we could get very high levels of CTL activity using a DNA-based vaccination approach – in HPV therapy. So I think it’s wonderful for Inovio and other developers in the DNA field to be looking at development of a broad range of vaccines — especially in the area of cancer.

Coupled with these advancements, another exciting development is the emergence of “checkpoint inhibitors” – PD-1 and PDL-1 antibodies – which researchers have employed to try to take the brakes off the cancer immunotherapy area. Whether it’s BMS’ work or Merck’s work, or Roche or MedImmune, just to name a few leading companies, what they’ve shown is that T-cell responses are clearly essential for dealing with cancer.

While those companies have focussed on getting the foot off the brakes by trying to develop these checkpoint inhibitors, there’s still a need for vaccine approaches that can drive strong T-cell responses, so we call it pressing on the accelerator.  What Inovio’s doing, and I can include the broader field of DNA vaccines, has been to press on the accelerator, to drive strong antigen-specific CD8 CTL responses. In this case, DNA vaccines can then make a meaningful impact in cancer, just as anti-PD-1 therapies are revolutionising cancer. And, perhaps, we’ll soon know if a combination therapy proves the best path forward.

An event last year stands as a milestone for Inovio and the field of DNA vaccines. In September, Roche signed a $400 million deal with Inovio to co-develop Inovio’s DNA vaccines for prostate cancer and hepatitis B. Overall it’s a validating event for the broader DNA vaccine field as well. We think we drew this interest because a DNA   platform affords the best safety profile whilst also being able to deliver on the immunology and efficacy that you want to see in cancer therapy.

The other exciting cancer developments are in the area of so-called engineered T cell approaches, where there are all these adoptive transfer approaches which have again shown that if you get the right kinds of T cells into cancer patients then you’re letting these T cells kill cancer cells and you are getting functional cures. But all of these approaches evolved from taking the patient’s own cells and then developing therapy that is highly individualised for the patient. On the other hand, DNA vaccines allow you to look at it in a more broad population-based approach, so we can think of population-based approaches to cancer just as conventional vaccines in the context of infectious diseases.

What are some of the current challenges to DNA vaccines? Is there anything holding us back?

There are clearly delivery challenges which have been part of the historical aspect for developing efficacious DNA vaccines, so that’s clearly the biggest challenge for the field. At Inovio, we’ve developed electroporation delivery technologies to address the delivery challenge. The other challenges for DNA vaccines are simply that we don’t have any licensed human vaccines as yet, so to a large extent, people working in DNA vaccines are really pioneering the development pathways, the regulatory pathways, and then the commercial pathways associated with developing a new platform. So although the platform itself is not that new, what we’re doing are sort of the first things anybody has done with DNA vaccines, to the extent that we’re driving the snowplough that others will follow.

 What do you predict will be some of the major changes within the vaccine industry in the next 12 months?

In the pharma industry as a whole, and then I guess within the context of the vaccine industry, there’s a lot of consolidation going on. So I think that’s going to drive some of the excitement in 2014. Even as new players are emerging in the biotech arena, in terms of big pharma, there continues to be consolidation. So that I see as a significant development in 2014.

The other, maybe from a broader, holistic aspect, is that vaccines have traditionally been looked at as preventative or prophylactic, but I see the focus shifting or greater attention being paid to therapeutic vaccines and immunotherapies. Science magazine already announced immunotherapies as a breakthrough of the year for 2013, and we’re going to see exciting news coming out of immunotherapies and therapeutic vaccines in 2014. Prevention and therapy are really two sides of the same coin, so I see companies dealing with both sides. I also think you’ll see that governments dealing with healthcare issues are going to have to pay attention to both the prevention as well as therapy as a regulator and a payor.

I predict we’ll see increased amounts of partnering in 2014. It’s been long recognised that a lot of today’s medical innovation is coming out of biotech companies, and in particular the smaller biotech companies, so as big pharma continues to expand on their pipeline and develop their late-stage product pipelines, I see early-phase biotechs or mid-stage biotechs playing an increasingly active role through partnering.

 There has been some concern among the general public about the safety and risk of vaccines. What positive steps can the industry take to improve public perception?

It is important that the value of vaccines continues to build and they’re appreciated in the broader public. I think the best thing the vaccine industry can do is to keep up the good work; keep producing and delivering these important breakthroughs. We need to keep talking about the benefits of vaccines and the lives saved.

One of the challenges, of course, from a public perception standpoint, is that it’s hard to prove a negative. What I mean by that is, take the case of flu: the only time we have a lot of excitement or a lot of media attention is when we have the threat of a pandemic, and yet flu vaccines have made a tremendous impact on keeping the disease burden low and trying to prevent cases of severe influenza and pandemics. It’s hard to communicate the message that “disease prevented” has a significant impact on our total healthcare spend.

So I think the vaccine industry, as well as industry organizations and the industry as a whole, have to keep focussing on that message — that vaccines preventing diseases is perhaps more important than treating disease. But at the same time, with the greater impact of therapeutic vaccines and immunotherapies, success in the therapeutic arena might well drive a change in public perception on the prevention side as well. So if people can equate the importance of vaccines in treating disease, then they would be able to better appreciate the greater impact vaccines have on preventing disease.

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