When cancer develops, it alters our genes in a way that leaves a permanent trace. For so long, these traces were a disguise that helped cancer to hide itself and evade our attempts to eradicate it from the body. But now, thanks to very rapid advances in technology, it is possible to sequence the entire human genome within a short period of time, yielding a trove of information that can help us to predict, understand and exploit these neoantigens through targeted immunotherapy with vaccines.
In this amazing podcast, discover this emerging area of cancer research and how neoantigens contribute to cancer immunotherapy research and help make cancer vaccines a possibility!
Joining the show is Dr. Kunle Odunsi, Executive Director, Center for Immunotherapy at Roswell Park, as he explains the role of neoantigens in immunotherapy for cancer.
Selected Podcast
The Role of Neoantigens in Immunotherapy for Cancer
Featured Speaker:
Learn more about Kunle Odunsi, MD, PhD
Kunle Odunsi, MD, PhD
Dr. Adekunle "Kunle" Odunsi is Deputy Director, Chair of the Department of Gynecologic Oncology, Executive Director of the Center for Immunotherapy and Co-Leader of the Tumor Immunology and Immunotherapy research program at Roswell Park Comprehensive Cancer Center.Learn more about Kunle Odunsi, MD, PhD
Transcription:
The Role of Neoantigens in Immunotherapy for Cancer
Bill Klaproth (Host): An emerging area of cancer research is on neoantigens, small proteins on the surface of cancer cells that are making personalized immunotherapies like cancer vaccines a possibility. And here to tell us about neoantigens for cancer immunotherapy, is Dr. Kunle Odunsi, Deputy Director at Roswell Park Comprehensive Cancer Center and also the Director for Immunotherapy at Roswell Park Comprehensive Cancer Center. Dr. Odunsi, thank you so much for your time today. So, let’s start right at the beginning. What are neoantigens?
Dr. Kunle Odunsi, MD, PhD (Guest): Well first of all, thanks for the invitation. Neoantigens are proteins that are made on cancer cells as the result of mutations in the cancer. As we all know, cancer cells are abnormal cells in the body and the way that they become abnormal is usually because of some genetic alterations. In other words, there is a mutation in certain genes and because of these mutations it leads to production of small proteins on the cancer cell surface that can now be recognized by the immune system. So neoantigens, if you think about it, it is like the cancer itself encoding the seed for their own disruption by the immune system.
Bill: Very Interesting. So, once someone has cancer, you take that mutated cell and from that you are able to make a vaccine, is that the concept?
Dr. Odunsi: So, the concept is when someone has cancer, we can actually take the cancer tissue and understand the mutational profile. We ask the question what are the genetic alterations in the cancerous tissue itself that can lead to neoantigens. And at Roswell Park, we have established a very robust strategy, a pipeline that allows us to predict when you take a cancer specimen to identify the neoantigens and potentially make vaccines from the neoantigens that would then destroy the cancer cell. Now let me point out that neoantigens are very unique because the holy grail of any cancer therapy is for you to try and destroy the cancer, but spare healthy normal tissues. I mean that’s the Holy Grail. We don’t want to cause side effects when we treat patients. If you think about it, conventional chemotherapy or even radiation therapy targets cancer cells, but may also affect normal cells. And that’s why frequently, patients have side effects from chemotherapy. Neoantigens provide the opportunity to specifically target genetic changes, alterations on the cancer cells alone because they will not be present in normal cells. So, we then use this information, one can now, you can envision how one can take that information and use it to manufacture vaccines that are personalized for that particular patient and by making the vaccines we generate immune responses against the neoantigens, in other words, immune responses against the cancer cells. So, that’s how it works.
Bill: So, you get very targeted treatment out of that. Dr. Odunsi, let me ask you this then. Do neoantigens, will they work on all types of cancer?
Dr. Odunsi: So, neoantigens are very promising, they are likely to work on almost every type of cancer, but one of the aspects that we have identified in the last few years is the fact that even when you mount a very strong immune response using neoantigens for example, the cancer cells tend to fight back. Okay, in other words, the cancer cells tend to develop ways to escape from immune attack, so when we use neoantigens, we envision that we will be using them together with additional treatment that will mitigate the ability of the cancer cells to fight back the immune system. So, neoantigens are likely to be useful for almost every cancer patient, but it will need to be used in conjunction with some additional therapies that we have that allows us to disable the ability of the cancer cells to fight back.
Bill: Got ya. So, say I get a form of melanoma. With potential neoantigen research, then you would potentially – how do these vaccines work? Would it be an injection, or do I take it by pill or how do you reintroduce that vaccine into the body to attack the specific cancer that a person may have?
Dr. Odunsi: So, there are several ways of making the vaccine. The approach that we have taken at Roswell that we are developing right now is to make, they are called peptides. These are fragments, short fragments of the protein that forms the neoantigen. So, we make this peptide and we mix it up and we give it, it is almost like getting a flu shot. So, it’s not a pill, it’s not an IV, it is simply like a flu shot and our approach is to give it to a patient every couple of weeks up to – for several treatments and we simply monitor those patients and see whether their cancer is shrinking.
Bill: This is just amazing Dr. Odunsi and I know you touched on research at Roswell Park Comprehensive Cancer Center. Can you talk to us a little bit more on how you are contributing to neoantigen research?
Dr. Odunsi: So, Roswell Park Comprehensive Cancer Center is contributing to neoantigen research in several ways. Number one we are focusing on neoantigen research by understanding how to identify neoantigens because not every mutation in the cancer cell produces neoantigen. So, we are conducting research on what is the best way to identify these neoantigens that are likely to be able to stimulate the immune system, generate robust immune attack against cancer cells. We are now taking that to develop a clinical protocol at Roswell Park that will be deployed across multiple cancer types including ovarian, including melanoma, and other cancer types. So, that’s number one contribution. Number two, we are also working on how to use neoantigens as a marker to predict who is likely to respond to some forms of immunotherapy. Because we and others have found that the neoantigen, the amount of neoantigens that are present in the cancer actually affect and they predict who is likely to respond or not to many forms of immunotherapy.
So, we have considerable research in that area and then the final area of research is to answer the question even when you identify the neoantigens, what is the best form of vaccination. Okay, I told you about one form of vaccination where we made the short peptide fragment, we make short fragments of the protein, these are called peptide vaccines, can we generate vaccines in a different way. So, we are exploring ability maybe to make the vaccines and put it in – you know mix it with some chemicals that can further boost the immune system. So essentially, what is the best way to deliver this vaccine. So those are some of the research questions that we are contributing to. It’s a very exciting area and we are very – also very excited about our ability to do all of these things at Roswell Park.
Bill: Gosh, you are right. That is so exciting and how soon do you think this will be rolled out to the general public. I know there’s a lot of research going on now but if you could look into the future, what do you think the future holds for us? Is this something five years, ten years down the road where this will be normal cancer treatment using neoantigens and immunotherapy?
Dr. Odunsi: First of all, some forms of immunotherapy are now already part of standard therapies. There has been recent approval by the FDA of many different kinds of immunotherapies in the last few years. Given the rapid pace at which scientific research in this area is ongoing, given the advances in technology, our ability to rapidly sequence cancer specimens from patients. I mean the technology has exploded over the last few years where we can sequence the whole genome of a person very, very rapidly. Putting all of that together, I think this field of using neoantigens is likely to be to get to the general public to go outside of clinical research and get into general public within a relatively time short frame. If I was to take a guess and place I want the audience to understand that this is just speculation, this is a guess, I will speculate that within the next 3-5 years or so, we might already see dramatic uptake and use of neoantigens as part of the mainstream of treatment of cancer patients.
Bill: Such good news in the fight against cancer. Dr. Odunsi, thank you so much for your time today and talking to us about neoantigens. For more information you can visit www.roswellpark.org that’s www.roswellpark.org. You’re listening to Cancer Talk with Roswell Park Comprehensive Cancer Center. I’m Bill Klaproth. Thanks for listening.
The Role of Neoantigens in Immunotherapy for Cancer
Bill Klaproth (Host): An emerging area of cancer research is on neoantigens, small proteins on the surface of cancer cells that are making personalized immunotherapies like cancer vaccines a possibility. And here to tell us about neoantigens for cancer immunotherapy, is Dr. Kunle Odunsi, Deputy Director at Roswell Park Comprehensive Cancer Center and also the Director for Immunotherapy at Roswell Park Comprehensive Cancer Center. Dr. Odunsi, thank you so much for your time today. So, let’s start right at the beginning. What are neoantigens?
Dr. Kunle Odunsi, MD, PhD (Guest): Well first of all, thanks for the invitation. Neoantigens are proteins that are made on cancer cells as the result of mutations in the cancer. As we all know, cancer cells are abnormal cells in the body and the way that they become abnormal is usually because of some genetic alterations. In other words, there is a mutation in certain genes and because of these mutations it leads to production of small proteins on the cancer cell surface that can now be recognized by the immune system. So neoantigens, if you think about it, it is like the cancer itself encoding the seed for their own disruption by the immune system.
Bill: Very Interesting. So, once someone has cancer, you take that mutated cell and from that you are able to make a vaccine, is that the concept?
Dr. Odunsi: So, the concept is when someone has cancer, we can actually take the cancer tissue and understand the mutational profile. We ask the question what are the genetic alterations in the cancerous tissue itself that can lead to neoantigens. And at Roswell Park, we have established a very robust strategy, a pipeline that allows us to predict when you take a cancer specimen to identify the neoantigens and potentially make vaccines from the neoantigens that would then destroy the cancer cell. Now let me point out that neoantigens are very unique because the holy grail of any cancer therapy is for you to try and destroy the cancer, but spare healthy normal tissues. I mean that’s the Holy Grail. We don’t want to cause side effects when we treat patients. If you think about it, conventional chemotherapy or even radiation therapy targets cancer cells, but may also affect normal cells. And that’s why frequently, patients have side effects from chemotherapy. Neoantigens provide the opportunity to specifically target genetic changes, alterations on the cancer cells alone because they will not be present in normal cells. So, we then use this information, one can now, you can envision how one can take that information and use it to manufacture vaccines that are personalized for that particular patient and by making the vaccines we generate immune responses against the neoantigens, in other words, immune responses against the cancer cells. So, that’s how it works.
Bill: So, you get very targeted treatment out of that. Dr. Odunsi, let me ask you this then. Do neoantigens, will they work on all types of cancer?
Dr. Odunsi: So, neoantigens are very promising, they are likely to work on almost every type of cancer, but one of the aspects that we have identified in the last few years is the fact that even when you mount a very strong immune response using neoantigens for example, the cancer cells tend to fight back. Okay, in other words, the cancer cells tend to develop ways to escape from immune attack, so when we use neoantigens, we envision that we will be using them together with additional treatment that will mitigate the ability of the cancer cells to fight back the immune system. So, neoantigens are likely to be useful for almost every cancer patient, but it will need to be used in conjunction with some additional therapies that we have that allows us to disable the ability of the cancer cells to fight back.
Bill: Got ya. So, say I get a form of melanoma. With potential neoantigen research, then you would potentially – how do these vaccines work? Would it be an injection, or do I take it by pill or how do you reintroduce that vaccine into the body to attack the specific cancer that a person may have?
Dr. Odunsi: So, there are several ways of making the vaccine. The approach that we have taken at Roswell that we are developing right now is to make, they are called peptides. These are fragments, short fragments of the protein that forms the neoantigen. So, we make this peptide and we mix it up and we give it, it is almost like getting a flu shot. So, it’s not a pill, it’s not an IV, it is simply like a flu shot and our approach is to give it to a patient every couple of weeks up to – for several treatments and we simply monitor those patients and see whether their cancer is shrinking.
Bill: This is just amazing Dr. Odunsi and I know you touched on research at Roswell Park Comprehensive Cancer Center. Can you talk to us a little bit more on how you are contributing to neoantigen research?
Dr. Odunsi: So, Roswell Park Comprehensive Cancer Center is contributing to neoantigen research in several ways. Number one we are focusing on neoantigen research by understanding how to identify neoantigens because not every mutation in the cancer cell produces neoantigen. So, we are conducting research on what is the best way to identify these neoantigens that are likely to be able to stimulate the immune system, generate robust immune attack against cancer cells. We are now taking that to develop a clinical protocol at Roswell Park that will be deployed across multiple cancer types including ovarian, including melanoma, and other cancer types. So, that’s number one contribution. Number two, we are also working on how to use neoantigens as a marker to predict who is likely to respond to some forms of immunotherapy. Because we and others have found that the neoantigen, the amount of neoantigens that are present in the cancer actually affect and they predict who is likely to respond or not to many forms of immunotherapy.
So, we have considerable research in that area and then the final area of research is to answer the question even when you identify the neoantigens, what is the best form of vaccination. Okay, I told you about one form of vaccination where we made the short peptide fragment, we make short fragments of the protein, these are called peptide vaccines, can we generate vaccines in a different way. So, we are exploring ability maybe to make the vaccines and put it in – you know mix it with some chemicals that can further boost the immune system. So essentially, what is the best way to deliver this vaccine. So those are some of the research questions that we are contributing to. It’s a very exciting area and we are very – also very excited about our ability to do all of these things at Roswell Park.
Bill: Gosh, you are right. That is so exciting and how soon do you think this will be rolled out to the general public. I know there’s a lot of research going on now but if you could look into the future, what do you think the future holds for us? Is this something five years, ten years down the road where this will be normal cancer treatment using neoantigens and immunotherapy?
Dr. Odunsi: First of all, some forms of immunotherapy are now already part of standard therapies. There has been recent approval by the FDA of many different kinds of immunotherapies in the last few years. Given the rapid pace at which scientific research in this area is ongoing, given the advances in technology, our ability to rapidly sequence cancer specimens from patients. I mean the technology has exploded over the last few years where we can sequence the whole genome of a person very, very rapidly. Putting all of that together, I think this field of using neoantigens is likely to be to get to the general public to go outside of clinical research and get into general public within a relatively time short frame. If I was to take a guess and place I want the audience to understand that this is just speculation, this is a guess, I will speculate that within the next 3-5 years or so, we might already see dramatic uptake and use of neoantigens as part of the mainstream of treatment of cancer patients.
Bill: Such good news in the fight against cancer. Dr. Odunsi, thank you so much for your time today and talking to us about neoantigens. For more information you can visit www.roswellpark.org that’s www.roswellpark.org. You’re listening to Cancer Talk with Roswell Park Comprehensive Cancer Center. I’m Bill Klaproth. Thanks for listening.