Category Archives: General

Immunotherapies – What’s all the Buzz About?

https://kids.frontiersin.org/article/10.3389/frym.2017.00040

The latest buzz in cancer research is talk of immunotherapies. The basis of immunotherapies is to empower the patient’s own immune system to mount an “attack” against cancer. This seems like a very enticing idea as it takes advantage of a natural process and avoids the classic cutting, burning and zapping of traditional cancer treatments.

Immunotherapies themselves encompass a wide range of treatment strategies. Vaccines can be used to stimulate immune cells to target foreign proteins found on cancer cells or viruses that are known to cause cancers. This type of strategy is currently used in preventative cancer vaccines against Human Papilloma Virus (HPV). HPV is the cause of virtually all cervical cancers, among others, and this vaccine is very effective at reducing the incidence of these cancers1.

Another type of immunotherapy is called adoptive cellular therapy, which involves taking immune cells, called T-cells, from the patient’s tumour, stimulating them to grow and divide, and re-injecting them into the patient. This method has been effective at treating patients with metastatic melanoma, illustrated by 50% response rates and a one-year survival rate of 60%. Such results are previously unheard of in this disease2. Technological advances have allowed researchers to modify these T-cells while they are out of the body so that they target a cancer-specific protein. These so-called chimeric antigen receptor T-cells (CAR T-cells) are a very hot topic in cancer immunotherapy at the moment and are being tested clinically for various blood cancers such as leukemia3.

Another heavy hitter in the ring of immunotherapies is immune checkpoint blockade (ICB). T-cells have natural mechanisms to dampen their own activity, ultimately to prevent autoimmunity. This involves a receptor on the T-cells (e.g. PD-1, CTLA-4) binding to its partner, which is expressed on other immune cells. Cancers often co-op this method by expressing the binding partner themselves, which turns off the T-cells and prevents anti-cancer activity. Then, the goal of ICB is to use antibodies to block these checkpoint proteins on T-cells from binding their partners. This keeps the T-cells “on” and ready to attack cancer cells. ICB has been dramatically effective in melanoma, as well as some lung and kidney cancers4–6.

Both adoptive cellular therapy and ICB have been approved by the FDA for various cancers and clinical indications. ICB antibodies such as nivolumab and ipilimumab have been approved for front-line treatment of metastatic melanoma7. Other cancers are playing catch-up, and most approvals to-date are for the use of immunotherapies only after a patient has failed at least two other treatment types. The hesitancy for full approval stems from a lack of efficacy in all patients.

A crucial next step is to investigate why some patients do respond while others don’t. There are many possible biological and immunological reasons why only some patients respond8, but the goal remains to develop a simple test that could be performed in clinic to predict response. Once this sort of test is validated, it will become faster and easier to approve and fund immunotherapies for patient subsets that are likely to respond.

Ongoing research into cancer immunotherapies is occurring at Queen’s University in the Division of Cancer Biology and Genetics of the Queen’s Cancer Research Institute. While some research focuses on developing tests to predict response to immunotherapies, other research focuses on making patients more responsive to treatment. Our hope is that we can harness the power of the immune system in as many cancer patients as possible.

References:

  1. Vonka, V. & Hamsíková, E. Vaccines against human papillomaviruses–a major breakthrough in cancer prevention. Cent. Eur. J. Public Health 15, 131-9 (2007).
  2. Rosenberg, S. A. et al. Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy. Clin. Cancer Res. 17, 4550-4557 (2011).
  3. Park, J. H. et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 378, 449-459 (2018).
  4. Robert, C. et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. N. Engl. J. Med. 372, 320-330 (2015).
  5. Lynch, T. J. et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J. Clin. Oncol. 30, 2046-54 (2012).
  6. Yang, J. C. et al. Ipilimumab (Anti-CTLA4 Antibody) Causes Regression of Metastatic Renal Cell Cancer Associated With Enteritis and Hypophysitis. J. Immunother. 30, 825-830 (2007).
  7. Drugs Approved for Melanoma. National Cancer Institute (2018). Available at: https://www.cancer.gov/about-cancer/treatment/drugs/melanoma. (Accessed: 10th December 2018)
  8. Sharma, P., Hu-Lieskovan, S., Wargo, J. A. & Ribas, A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 168, 707-723 (2017).

This article was written by Alison Moore, an M.Sc. Candidate in the Department of Pathology and Molecular Medicine, and part of the Cancer Research Institute at Queen’s University.

Women in Cancer Research – International Women’s Day 2017

March 8th is International Women’s Day, a day in which we celebrate the great achievements of women in the world in addition to recognizing that gender parity has not yet been reached worldwide. In Canada, women account for almost half (39%) of university graduates with a STEM (science, technology, engineering, mathematics) degree, however, only 22% work in the field1,2. This article will profile some of the outstanding female scientists working in the cancer research field here at Queen’s University.

 

Dr. Harriet Feilotter is an associate professor in the Department of Pathology & Molecular Medicine as well as Laboratory Director of Molecular Genetics and Service Chief of Laboratory Genetics at Kingston General Hospital. Feilotter runs both a basic science and a clinical lab. Her research lab aims to optimize detection and quality control of putative biomarkers for diseases so they can hopefully be applied in a clinical setting. Feilotter began her science career here at Queen’s, being inspired by Biology professor Dr. Virginia Walker. “Almost all of my professors were male but the most influential professor was Virginia Walker. She was so enthusiastic about science and completely lit a fire under me to pursue molecular genetics”. While Feilotter feels that the human genetics field is well-populated with women and has never felt her gender affected how her work was viewed, she has experienced some prejudice. “I’ve had someone say ‘I don’t know how you can be a mother and a scientist – but I guess if you just do an average job at both, you can get it done’. Women need to figure out that balance, and we’re effective at it”. The most valuable lesson she’s learned over her career is to listen. “I’ve learned how to listen to what other people are trying to say, even when I have a burning idea I want to get out. That took me a long time to learn. It’s quite easy to be dismissed as a female voice unless you have a thoughtful approach to how you’re going to lead things.” Feilotter advises to young women interested in pursuing a career in science, “There are no barriers. You may perceive them as barriers, but if you excel at what you’re doing, you will be supported in science. I don’t see women being kept down, but I see women tripping themselves up, for example, exhibiting impostor syndrome. If you want to do it, if you believe in yourself, you can do it.”

 

Dr. Anne Petitjean is an associate professor and researcher in the Department of Chemistry. Her research currently focuses on the development of small molecules that can be used to target a specific folding pattern of DNA related to cancer progression. Petitjean grew up in France, and from a young age was interested in science. “From age 8 I had a passion for research. I also loved art. For me, chemistry was the common feature. Chemistry lends itself well to artistic expression and creativity; you’re creating a mini sculpture in your flask, you hold the design.” When applying for her PhD she reached out to Nobel laureate Dr. Jean-Marie Lehn despite having little confidence of being accepted into his lab. “I’m a shy person but there was this unconscious sense of what I could achieve. I sent message after message, and even called six times the morning that my application was due; I thought to myself, what are you doing bugging a Nobel laureate six times in the same morning?” Dr. Lehn ultimately accepted her into his lab where she published 15 papers from her PhD work. “This changed my path completely. My unconscious just took over – there must be some aspect of brain that knows more about what we should be doing.” Petitjean’s advice: follow your heart and be yourself. “If you follow your heart, you’ll get where you need to go. Be true to yourself and it will take you somewhere where you’re happy. You may not fit the frame where you envision being but twisting yourself and trying to force yourself to it, it will break.”

 

Dr. Leda Raptis is a professor in the Department of Biomedical and Molecular Sciences and a researcher in the Division of Cancer Biology & Genetics at the Queen’s Cancer Research Institute. Originally from Greece, Raptis grew up in an environment where family members and teachers discouraged women from pursuing a science career. “My mother would ask ‘why study since you’re going to get married and quit?’ and my father always said that women aren’t good in mathematics”. But Raptis was good at math, often getting the top mark on her exams. When she went to her father with this he said “you’re a woman, but you have a man’s brain”. She went on to attend university, being only one of a dozen women in a class of 400. Raptis faced gender discrimination throughout her university career, one of the worst offenses being when a male professor attempted to kiss her when she approached him for a reference for graduate studies. In 2010, after establishing a successful career in cancer research, she found a lump in her breast – grade 3 breast cancer. Her tenacity for research is exemplified by the fact that she continued to research as much as she could throughout physically draining chemotherapy treatments. After two mastectomies she has been cancer-free and has developed a focus on breast cancer research in her lab. “Often times, when women fail, they give up. Keep going. There are going to be setbacks, again and again, but you must do your darndest”.

 

Dr. Harriet Richardson is an associate professor in the Department of Public Health Sciences and an epidemiologist in the Division of Cancer Care and Epidemiology at the Queen’s Cancer Research Institute. Originally studying the incidence of human papillomavirus (HPV) infections, Richardson now studies the role of environmental factors on breast cancer risk as well as interventions to prevent the occurrence of breast cancer. Richardson’s mother was an academic and an active feminist. “When I was young, she used to take my brother and I to Women’s Rights demonstrations in London, England and Montreal. I was pressured to have a career first and then think about starting a family. To quote my mother, ‘Over my dead body will you have a baby before you finish your PhD!’”. Richardson’s early HPV work was a stepping stone that led to the approval of the HPV vaccine and she has also been involved in a landmark breast cancer prevention trial; however, her proudest moment in science is in the role of a mentor to her students (who are all smarter than she is, she says). “Knowing that I might have a small role in inspiring the next generation of Canadian epidemiologists and clinical scientists is incredibly rewarding.” Richardson’s advice, “Find supportive research environments to work in and try to build collaborations with people you like. Know that finding a life balance will always be a struggle, and you have to work at it every day. And although it sounds a cliché, try not to sweat the small stuff and treat everyone with respect and compassion.”

 

Dr. Madhuri Koti is an assistant professor in the Department of Biomedical and Molecular Sciences and a researcher in the Division of Cancer Biology & Genetics at the Queen’s Cancer Research Institute. Her research focuses on the immune response to chemotherapy in cancer. Koti originally trained to be a veterinarian, earning her DVM in India. “As a young girl I wanted to be a doctor. If I couldn’t be a human doctor, I’d be a veterinary doctor”. While Koti felt no societal pressures to pursue a more “traditionally feminine” career, she did recognize that veterinary school was not popular among women in India, being one of only six women in a class of 76. Near the end of her veterinary training she gained an interest in immunology and went on to earn a PhD in immunology from the University of Guelph. Koti has since focused her research efforts on ovarian cancer as the immune response plays a large role in that cancer. “It’s important to work towards your dreams and never give up on them. You have to be honest to yourself. Be critical. Believe.”

 

References

  1. Hango, D. Gender differences in science, technology, engineering, mathematics and computer science (STEM) programs at university. Stat Can. 2013; 75-006-X: 1-11.
  2. Dionne-Simar D, Galarneau D, and LaRochelle-Côté S. Women in scientific occupations in Canada. Stat Can. 2016; 75-006-X: 1-13.

 

This article was written by Jen Power, a M.Sc candidate in the Department of Pathology and Molecular Medicine, and part of the Collaborative Graduate Program in Cancer Research at Queen’s University.

Vaccination for yellow fever – a new way of reducing breast cancer risk?

New research has unveiled that breast cancers produce proteins very similar to those made by the virus that causes yellow fever. Since vaccines have been created to prevent yellow fever, there is a potential that the vaccine could also be used to prevent breast cancer.

Scientists have been trying to find ways to develop vaccines to target potential cancer cells for years. However, only a handful have been successfully implemented, such as the vaccine for human papillomavirus (HPV), which helps prevent HPV infections that cause cervical and head and neck cancers1. Few other cancer types are caused by viruses, making them difficult to target with vaccines2.

How do vaccines work?

Vaccines introduce a small amount of a virus into your system – not enough to cause symptoms, but enough to make your immune cells familiar with foreign particles3. In response, the body develops an army of immune cells that are specifically designed to target that virus. After immunization, the presence of any viral particles in the body will lead to the mobilization of the targeted immune cell army and destruction of the virus before infection sets in3.

Yellow fever vaccine may prevent breast cancer

A study published in the European Journal of Cancer Prevention showed that the yellow fever vaccine may be linked to a decrease in breast cancer risk in women aged 40-544. Researchers in Veneto, Italy looked back at medical records of women who received the yellow fever vaccine and looked for breast cancer diagnoses after vaccination. Among 12,804 women who received the vaccination, 187 cases of breast cancer were found. Women who received the vaccine between the ages of 40 and 54 experienced the greatest decrease in breast cancer risk with a 54% reduction in breast cancer incidence following administration of the yellow fever vaccine4. The researchers therefore proposed that the vaccine could help protect against breast cancer.

Retroviruses in breast cancer

Breast cancer itself has not been linked to viral infection. However, breast cancers produce human endogenous retroviral (HERV) proteins that closely resemble the proteins produced by yellow fever. Other cancers including melanoma, ovarian cancer, and prostate cancer have also been shown to express these HERV proteins5. HERVs are remnants of ancestral infections that have become incorporated in our DNA and passed down through several generations.  They have been maintained as part of our cells because they serve some function that is beneficial to human physiology. Approximately 8% of our DNA can be traced back to HERVs5.

Using the yellow fever vaccine to target breast cancer

The yellow fever vaccine was first developed in 1937 to target the yellow fever virus, which causes liver dysfunction and yellowing of the skin (hence the term yellow fever)3. When vaccinated, the body develops an army of immune cells called T cells to target the yellow fever virus. Because of the similarities between yellow fever and the HERVs produced in breast cancer, the army of T cells will also recognize and destroy any HERV-producing breast cancer cells3.  Think of it in terms of languages. The T cells have been trained to understand English, a language that is spoken by both the yellow fever virus (with an American accent) and the breast cancer HERVs (with an Australian accent). Regardless of the accent, the T cells will still be able to recognize and understand both types of proteins. This is called “cross-reactivity”. However, if the T cells meet another type of virus speaking a different language, for example HPV speaking French, the T cells will not be able to understand or act on the signals from that virus.

Next steps

While the findings in this study are interesting, a vaccine for breast cancer is still far from reality. More active studies are necessary in order to establish the relationship between breast cancer and the vaccine for yellow fever as well as to determine the mechanism by which this vaccine affects breast cancer risk. This could be in the form of a clinical trial, with some women receiving the vaccine and others receiving a placebo4. If the relationship is real, it would be very easy to implement this vaccine because it is already mass-produced and has been administered more than 540 million times4. This finding is therefore an exciting step forward in the world of cancer vaccines.

References 

  1. Psyrri, A. & DiMaio, D. Human papillomavirus in cervical and head-and-neck cancer. Nat. Clin. Pract. Oncol. 5, 24–31 (2008).
  2. Tabi, Z. & Man, S. Challenges for cancer vaccine development. Advanced Drug Delivery Reviews 58, 902–915 (2006).
  3. Barrett, A. D. & Teuwen, D. E. Yellow fever vaccine – how does it work and why do rare cases of serious adverse events take place? Current Opinion in Immunology 21, 308–313 (2009).
  4. Mastrangelo, G., Pavanello, S., Fadda, E., Buja, A. & Fedeli, U. Yellow fever vaccine 17D administered to healthy women aged between 40 and 54 years halves breast cancer risk. Eur. J. Cancer Prev. 1 (2016).
  5. Downey, R. F. et al. Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice? Int. J. Cancer 137, 1249–1257 (2015).

This article was written by Catherine Crawford-Brown, a M.Sc candidate in the Department of Pathology and Molecular Medicine, and part of the Collaborative Graduate Program in Cancer Research at Queen’s University.

Kingston’s RIOT continues to expand its youth outreach involvement with the local community

The Kingston Research Information Outreach Team (RIOT) has previously engaged in many outreach opportunities highlighting various aspects of cancer (ie. prevention, biology, treatment, local research & career opportunities), including through interactive workshops for elementary students at the Frontenac, Lennox & Addington Regional Science Fair, and hands-on activities for members of all ages of the Kingston community at Science Rendezvous. Over the past few months, RIOT has expanded its outreach involvement to include additional organizations of the Kingston community, including the Boys and Girls Club of Kingston & Area, and the local chapter of the Girl Guides of Canada.

RIOT members had the unique opportunity to lead interactive, hands-on activities for participants (aged 5 – 10 years old) of a Girl Guide Summer Day Camp at Carruthers Point in early August 2016. As part of this workshop, the girls were exposed to a broad range of cancer-related topics, including prevention, probability, ongoing research approaches, and future job possibilities. Additionally, on Monday, October 3rd, 2016, a group of volunteers from Kingston RIOT ran an afterschool seminar for students in grade 8-12 at the Boys and Girls Club of Kingston & Area. During this hour-long session, students learned the difference between risk factors (ie. things that promote cancer) and protective factors (ie. things that prevent cancer). In an activity coordinated by volunteer Sarah Nersesian, each group of students was assigned a plastinated organ containing a tumour. Students had to identify the organ, show where it is located in the body, and describe the cancer. The samples used in this activity were graciously donated to Queen’s University to be used as teaching tools and were plastinated to preserve the integrity of the tumour. Students saw firsthand the kinds of tumours that Terry Fox had (ie. bone cancer and metastatic lung cancer) and learned the differences between cancer types (ie. primary versus secondary tumours and their different appearances). A career discussion led by member Maximilian Niit concluded the session. Students were excited to learn about the range of career opportunities available in the health sciences and which jobs best fit with their personalities.

Through these youth outreach sessions, we hope local students gained some appreciation for what cancer is, how it can be prevented, and how they can participate in the health sciences in the future.

This article was written by Catherine Crawford-Brown, a M.Sc candidate in the Department of Pathology and Molecular Medicine, and part of the Collaborative Graduate Program in Cancer Research at Queen’s University.