By Nora Disis, MD
Obesity is a major problem and a major cause of cancer, and there's a particular type of obesity called inflammatory obesity where patients develop metabolic dysfunction. This dysfunction is really mediated or caused by immune cells and the type of immune cells it's caused by are CD8 T-cells. The CD8 T-cells begin to recognize immunogenic proteins in fat, and they proliferate and compete for limited resources in the body fat. They become dysfunctional, and this is one of the ways cancer grows. Even if people lose body weight, they may not fully correct their metabolic dysfunction, and for this reason, we developed a adipocyte vaccine that would prime the immune system to recognize those inflammatory fat cells and drive the opposite type of T-cell, then a CD8 T-cell to the fat A type II T-cell. These type II T-cells secrete cytokines like IL-10 that abolish that CD8 t-cell function and type I cytokine secretion.
We developed the adipocyte vaccine. The proteins in the vaccine are highly homologous between mouse and man. We were able to immunize mice. They could develop immune responses of the IL-10 secreting T-cell phenotype. All the antigens in the vaccine, and then we took it to testing in a model of obesity. So we took mice, we fed them a western diet, high fat, high sugar. The mice became obese, and at the time they became obese. We let one group go and one group we gave the Adipocyte directed vaccine and our endpoint was to see if we could prevent them from developing diabetes. And the adipocyte vaccine worked, when you looked at insulin resistance (insulin sensitivity) and glucose control, the obese animals were pre-diabetic and the animals that got the vaccine had reversed their glucose control to almost normal (E.g. no insulin resistance), lean mice and when we looked at their fat, we had reduced the level of those CD8 T-cells. Now the next step was to see if that vaccine would prevent breast cancer. We went into an animal model that developed breast cancer. When you make this animal model obese, the breast cancer is much more aggressive and by 30 weeks all animals have very large breast tumors. So we took those animals, we made them obese in some animals, we just let them go, and in some animals, we gave them the adipose directed vaccine. And at 30 weeks, all the animals that received nothing had large tumors that were about to take their lives. And 60% of the animals in the adipocyte vaccine group had no evidence of disease.
So this is the first evidence of a vaccine designed to really target. A risk factor for cancer, and we're working on trying to get the vaccine to the point where we can put it into clinical trials.
Breast cancer was a good model for us because we had transgenic mice that would spontaneously develop breast cancer, and we had previously shown that making the mice obese would make their cancer more aggressive, but there is no reason why this adipose directed vaccine would not be able to limit risk for any of the cancers that are really associated with obesity, such as colon cancer, prostate cancer, or endometrial cancer. So one of our goals is to move into other cancer models to see if the vaccine can prevent the development of those cancers as well as to determine what the safety of the adipocyte vaccine is overall.
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The common questions that we get from colleagues about this data "When we present it is what type of patient population would you take the vaccine into?" And I think where we would start would be in those patients who have a risk of breast cancer or colon cancer, or prostate cancer who have pre-diabetes, because we do have evidence to support that the vaccine would potentially be able to prevent further progression of pre-diabetes. Another common question we get is, "Is there a blood test or a biomarker that might indicate those patients at highest risk where we should prioritize them to get such a vaccine?" And I think that's an excellent question. It's an area of research for us, we're trying to look in animal models right now to see if we can identify a blood marker that would indicate an animal who was obese who would have a more accelerated course of breast cancer, let's say. But it's a question that really needs to be addressed in humans. And we're looking at some very large data sets of blood samples that have been collected in women who are obese and developed breast cancer compared to women who are obese and did not develop breast cancer. And we hope by probing those serum samples, we'll be able to come up with such a biomarker.
In terms of timing, we hope the adipocyte vaccine will, I impact clinicians soon. We're on kind of a three year timeline to get this vaccine into the clinic. And we're having a lot of talks with regulators about how that vaccine would move into clinic as a vaccine to prevent, a very serious risk factor for cancer.
Right now we're in the phase where we're really looking at the animals long term, seeing whether the vaccine will reduce the weight of animals in the long term, giving the adipocyte vaccine over an extended period of time and looking to see if there are any side effects. So far we haven't seen any, so hopefully in three years, it'll be in clinical trials and we'll be able to get a handle of how long clinical development will take at that time.
The biggest takeaway I'd like to leave about this type of vaccination is that obesity isn't as simple as lose weight, exercise, in inflammatory fat in patients at the highest risk of developing cancer is metabolic dysfunction, and that needs to be corrected. And metabolic pathways in metabolic dysfunctions are really a primary area where we should be focusing on giving patients better tools to have a physiologic effect to correct these metabolic defects and allow them to reduce their risk of the development of cancer while they themselves develop a healthier lifestyle.
Breast cancer is the most commonly diagnosed cancer in women worldwide, and although many advances have been made in its diagnosis and treatment, there is still a need for new approaches to reduce the incidence and mortality of this disease. One such approach currently being investigated is adipocyte-directed vaccination, which has shown promise in reducing the risk of breast cancer.
Adipocytes, or fat cells, have been shown to play an important role in the development and progression of breast cancer. Adipocytes can secrete hormones and other molecules that promote the growth and survival of cancer cells, and they can also provide a physical barrier that protects cancer cells from chemotherapy and radiation. Therefore, targeting adipocytes may be an effective way to prevent the development and spread of breast cancer.
Adipocyte-directed vaccination is a novel approach that involves vaccinating against specific molecules that are expressed by adipocytes in breast tissue. These molecules are known as adipocytokines, and they have been shown to play a role in breast cancer development and progression.
One adipocytokine that has been studied extensively is leptin, which is a hormone that regulates appetite and metabolism. Leptin is also produced by adipocytes, and high levels of leptin have been associated with an increased risk of breast cancer. Vaccines that target leptin have been shown to reduce the growth and spread of breast cancer cells in preclinical models, suggesting that they may be effective in preventing the development of breast cancer.
Another adipocytokine that has been targeted in vaccine development is adiponectin, which is a hormone that regulates glucose and lipid metabolism. Adiponectin levels are often lower in obese individuals, who are at increased risk of breast cancer, and vaccines that target adiponectin have been shown to reduce the growth of breast cancer cells in preclinical models.
Adipocyte-directed vaccination has several advantages over traditional cancer vaccines. First, because adipocytes are present in breast tissue even before cancer develops, targeting adipocytes could prevent cancer from developing in the first place. Second, adipocyte-directed vaccines may be less toxic than traditional chemotherapy and radiation, which can damage healthy tissues in addition to cancer cells.
Despite these promising results, adipocyte-directed vaccination is still in the early stages of development, and more research is needed to determine its safety and efficacy in human clinical trials. However, if successful, this approach could provide a new and effective way to prevent breast cancer in women at high risk for the disease, particularly those who are obese or have a family history of breast cancer.
In conclusion, adipocyte-directed vaccination is a promising new approach to reducing the risk of breast cancer by targeting adipocytes, which play a critical role in breast cancer development and progression. While still in the early stages of development, this approach has shown promise in preclinical models and may provide a less toxic and more effective way to prevent breast cancer in women at high risk for the disease.
Adipocytes, or fat cells, play a crucial role in the development and progression of breast cancer.
Adipocytes can secrete hormones and other molecules that promote the growth and survival of cancer cells, and they can also provide a physical barrier that protects cancer cells from chemotherapy and radiation.
Targeting adipocytes may be an effective way to prevent the development and spread of breast cancer.
Adipocyte-directed vaccination is a novel approach that involves vaccinating against specific molecules that are expressed by adipocytes in breast tissue.
Adipocytokines, such as leptin and adiponectin, have been identified as potential targets for adipocyte-directed vaccines.
Vaccines that target leptin and adiponectin have been shown to reduce the growth and spread of breast cancer cells in preclinical models.
Adipocyte-directed vaccination could provide a less toxic and more effective way to prevent breast cancer in women at high risk for the disease.
Adipocyte-directed vaccination may be particularly effective in preventing breast cancer in obese women, who have higher levels of adipocytokines.
More research is needed to determine the safety and efficacy of adipocyte-directed vaccines in human clinical trials.
Adipocyte-directed vaccination represents a promising new approach to reducing the risk of breast cancer by targeting the role of adipocytes in the disease.
Nora Disis, MD - About The Author, Credentials, and Affiliations
Nora Disis, MD, is a distinguished physician-scientist with a focus on cancer immunotherapy. She is in charge of the University of Washington's UW Medicine Cancer Vaccine Institute as of right now. Dr. Disis went to the University of Nebraska Medical Center to get her medical degree and did her residency in internal medicine at the University of Iowa. She then did a fellowship in medical oncology at the University of Washington, where she has been a faculty member since 1993.
Dr. Disis is a well-known leader in the field of cancer immunotherapy. He has done a lot of research on how cancer vaccines work and how the immune system reacts to cancer. Her research has been mostly about finding antigens that are linked to tumors and using these antigens to make new cancer vaccines. She has also helped come up with new ways to treat cancer with immunotherapy, like adoptive T cell transfer and checkpoint inhibitors.
Dr. Disis has won many awards and honors for her work in the field of cancer immunotherapy. These include the William B. Coley Award for Distinguished Research in Tumor Immunology from the Cancer Research Institute and the Women in Science Award from the Seattle Chapter of the Association for Women in Science. She has written more than 300 scientific papers and has served on many national and international committees, such as the Board of Scientific Counselors of the National Cancer Institute and the Oncologic Drugs Advisory Committee of the FDA.
Dr. Disis is dedicated to improving cancer immunotherapy and making things better for cancer patients. She continues to lead groundbreaking research into the development of cancer vaccines and other immunotherapeutic approaches. She also acts as a mentor to the next generation of cancer immunotherapy researchers.