The Promise of Neoantigens for Personalized Cancer Vaccines
Kaitlyn Waters:
Hi everyone. Welcome to this podcast from Cambridge Healthtech Institute for the Protein Engineering Summit, which runs May 1st to the 5th, 2017 in Boston, Massachusetts. I'm Kaitlyn Waters, associate conference producer. We have with us here today one of our speakers from the Adoptive T-Cell Therapy Conference, Phillip Arlen, M.D., President and CEO at Precision Biologics. Dr. Arlen, thank you for joining us.
Phillip Arlen:
Thank you, Kaitlyn for having me here today.
Kaitlyn Waters:
Your work focuses specifically on gastrointestinal cancers. Where do you think we are in terms of personalized diagnostics for these cancers, and what will take to see these be used in routine clinical practice?
Phillip Arlen:
That's a very good question. As you know, with medicine today, we're moving from a general Betty Crocker cookbook type of treatment and diagnostics for patients to a more personalized approach. When you look at diagnosing GI type of cancers, traditionally what we've been doing for colon-rectal cancers has been the most appropriate way of using diagnostics and colonoscopy/fecal occult blood testing. There's been some new molecular markers that have been coming to help make those diagnoses. However, when we look at the personal diagnostics for therapies, I think there's a big trend now in terms of the genomic and proteomic approaches to these. If we're looking at where this may be going, there's a lot of scientific information now that's able to show differences in obviously different individuals. By being able to use personalized diagnostics for the different types of cancers and focusing on GI cancers, we'll be able to not only be able to diagnose these individuals better, but to be able to come up with the proper treatment strategies that may benefit those individuals more than just a generalized approach.
Kaitlyn Waters:
How do you see the role of neo-antigens and cancer vaccines fitting into the immunotherapy pipeline moving forward?
Phillip Arlen:
Immunotherapy over the past five years has been a very exciting area. The biggest progress has been made in the area of checkpoint inhibitors which is really turning off the brakes of immuned-out regulations. Those types of therapies allow for the immune system to work longer. It also helps target the different types. There have also been approaches with CAR T-cells, which are directing T-cells towards attacking tumors. However, what we're finding is that the immune system, as science is progressing, is a lot more complex than just having those types of strategies. Obviously there are targets that are found on tumors and what we're finding is that these targets that are found on tumor cells are not found on cells that are of normal cells. These are what we consider neo-antigens, so they're basically targets that are found on the actual cancer cell that get expressed during cancer but are not necessarily found on normal cells. These make very good targets and there's a lot of data, at least scientific data now, to suggest that using these neo-antigens and targeting them for cancer vaccines can be an approach that may come into play with the other types of immunotherapies and make those work better and give better outcomes for individuals with cancer.
Kaitlyn Waters:
What do you see are some of the biggest challenges in working with neo-antigens?
Phillip Arlen:
One of the biggest challenges is really two-fold. Number one is trying to identify what those neo-antigens are and there are technologies and there are companies now that are able to implement the technologies, being able to screen cancer using genomic approaches versus healthy tissue in individuals. Using bioinformatics, they can predict certain targets that may be worth creating vaccines in particular individuals. One of the biggest challenges in that approach is that since we're really working with computer systems and informatics, we're not really clear if those actual targets or neo-antigens that we're using in vaccines are the proper targets to be used for the vaccines, meaning, are they functional? When we look at computer programs that say these peptides, may bind better in activate T-cells, we're not sure, at least at this current point in development, whether or not these are actually really functional, meaning when you identify the antigens and you put them into a vaccine, when you bring them into patients, will these really cause a clinical benefit? Is it possible that these certain antigens may actual down-regulate or turn off the immune system? There's still a lot that needs to be found out about how to do not just target neo-antigens, but determine what the function of those particular antigens are and whether or not, by targeting them, they would benefit individuals.
Kaitlyn Waters:
Where do you see the future of immunotherapies?
Phillip Arlen:
Immunotherapies, as our scientific ability to evaluate what's happening in the clinic, evaluate being able bring information from patients into the laboratory and bring that forward, I think where the excitement in the immunotherapies is really the combination of approaches, and I think we're really understanding, just like other ways of treating patients, that just because there's a drug that has a benefit or a target or approach that may be beneficial, cancer in patients is complex. There are mechanisms where the tumor can even an active drug that's shown in the laboratory doesn't work because the cancer itself has ways of turning off the ability of the drugs to work. I think the combination approaches are really where the excitement comes, meaning that if you take a vaccine, for instance, using a neo-antigen and you're able to get an immune response against that, by coming in with other therapies, that's just a checkpoint inhibitor, which can allow for the immune system to work longer. Come in with other therapies that may knock out tumor suppression mechanisms, where the cancer's actually down-regulating the immune system, so coming in with a drug that may inhibit the cancer from being able to escape the immune response. By combining all of this together, this is really where I think immunotherapy is going to really see its true potential in the future.
Kaitlyn Waters:
Dr. Arlen, thank you for your time and insights today.
Phillip Arlen:
Thank you so much, Kaitlyn.
Kaitlyn Waters:
That was Phillip Arlen, M.D., President and CEO at Precision Biologics. He'll be speaking at the Adoptive T-Cell Therapy Conference at the upcoming Protein Engineering Summit which runs May 1st to the 5th, 2017 in Boston, Massachusetts. If you'd like to hear him in person, go to www.pegsummit.com for registration information and enter the key code PODCAST. I'm Kaitlyn Waters. Thank you for listening.