Immunotherapy

Success Measurement

  • Reduce the incidence and mortality of HPV-related gynecological cancers
  • Increase in the uptake of Pap to HPV testing and HPV vaccinations in BC and worldwide
  • Improve understanding of the present to progression of the HPV virus to cervical cancer
  • Increase the number of immunotherapy trials available to gynecological cancer patients in BC
  • Develop first-in-class gene-engineered cell based immunotherapy for ovarian and related cancers

Strategic Initiative

A revolution is underway in Canada’s health research landscape. The speed of discovery, convergence of disparate research fields and evolving health needs of Canadians are creating a number of significant, mutually reinforcing trends that are changing the way health research and knowledge translation are being conducted. Technological advances in health and health care research have tremendous potential for refining and expanding options for clinical practice and care, for improving understanding of human development and disease, and for conceptualizing novel upstream prevention pathways to improve population health. One of these is to pursue the development of immune-based prophylactic and therapeutic approaches for cancer. Chemo and radiotherapy are effective in reducing tumor size, but they unfortunately also affect healthy cells. The human immune system is a more accurate weapon, which has evolved to recognize and eliminate tumour cells. However, cancer cells employ a range of different strategies to confuse and thwart the immune system. Immunotherapies, which help stimulate the immune system to better identify specific cancer cells, show promising results and by all measures will revolutionize oncology practice.

I. Prevention

HPV is the most common sexually transmitted infection and three out of four women who are sexually active are at risk of contracting the virus. In most women, it clears on its own, while for others it becomes a persistent infection which leads to precancerous lesions. An HPV infection can cause cervical, vulvar, vaginal, anal, mouth and throat cancer in women. Prophylactic vaccination induces an immune response which produces HPV-neutralizing antibodies that are capable of preventing initial infections; hence prevent the development of the cancers. To further develop the use of prophylactic vaccinations, GCI scientists in collaboration with the BC HPV Research Group are engaged in multiple studies dedicated to understanding HPV vaccine efficacy and the immunological response to this vaccine.

  • Because the vaccines appear to produce such a robust immune response with such comprehensive protective ability, it was postulated that the expensive and labour intensive 3 doses at 0, 2 and 6 months may not be required and that 2 doses at 0 and 2 months might be sufficient. Preliminary data from this study shows that in 9-11 year old girls, two doses of the vaccine generates a superior antibody response in comparison to three doses of the vaccine in 16-26 year old girls. Today, our BC scientists and clinicians are examining if 1 dose is as or more effective for Canadian girls. This is critical information that will inform future research and vaccine policy decisions.
  • Because the vaccines appear to produce such a robust immune response with such comprehensive protective ability, it was postulated that the expensive and labour intensive 3 doses at 0, 2 and 6 months may not be required and that 2 doses at 0 and 2 months might be sufficient. Preliminary data from this study shows that in 9-11 year old girls, two doses of the vaccine generates a superior antibody response in comparison to three doses of the vaccine in 16-26 year old girls. Today, our BC scientists and clinicians are examining if 1 dose is as or more effective for Canadian girls. This is critical information that will inform future research and vaccine policy decisions.
  • Although these vaccines appear to be highly efficacious, it is not entirely understood how they work and what level or nature of immune response is required for protection against HPV infection. It is understood that the immune mechanisms involved in protection are very different than those involved in clearance. This knowledge gap is being addressed by studies ongoing with the goal of understanding the mechanisms underlying vaccine-induced protection. As a part of the ongoing evaluation of the role of these vaccines in different populations it is also being tested in women from 26-45 years old.
  • One of the questions regarding the worldwide rollout of the HPV vaccine is whether it will be safe and effective for women in countries with high rates of HIV infection where immune response may be drastically altered. A four-year investigation into the safety, effectiveness, and seroresponsiveness (response to a vaccination) of HPV vaccination in HIV positive girls and women has been initiated. This is one of the first studies to be done in this area and the results will inform appropriate use of the vaccine in this population. This study is being coordinated at the Women’s Health Research Institute (WHRI) in BC and includes 16 recruitment sites across Canada, 7 clinical and basic science laboratories across North America, and 41 Investigators from Canada, the United States, and Europe. This study will also lead to substantive developments in the area of serotesting (diagnostic identification of antibodies) to determine the nature of the immune response to natural infection and to the vaccine.
  • A large scale clinical trial evaluating tolerability, immunogenicity, and efficacy of a prophylactic multivalent HPV vaccine. This study has an allocation of over 400 women and will be critical in understanding the efficacy of a new 9-valent vaccine over the short and long term and represents the opportunity for BC to be seen as an effective site for large scale clinical trials.

II. Treatment

Cancer immunotherapy is based on the concept of stimulating the patient’s own immune system to recognize and destroy tumour cells. The main foot soldiers in the battle between immunity and cancer are T cells: small, powerful white blood cells that have the remarkable ability to kill cancer cells selectively, within minutes of contact. Immunotherapy is yielding remarkable outcomes for specific cancer patients, but the reality is that immunotherapy is highly effective against some cancers, but not against the majority. This incentive is making it an exciting and active area of oncology research today which may provide an option to existing treatments for a broader range of cancer types.

Adoptive Cell Therapy (ACT) is the treatment paradigm with the greatest potential and hence forms the basis of one of the research programs. Specifically, it is the development of personalized ACT approaches where patients are directly infused with their own T cells that have been conditioned or engineered to recognize and attack their cancer. The phenomenal breakthroughs of ACT against leukemia and melanoma are fuelling intense interest in expanding this approach to gynecologic cancers. Building on these successes, our team of internationally recognized Canadian researchers, in collaboration with partners across Canada and around the world, are creating an innovative portfolio of strategies that will take ACT to new heights, creating new treatment options for cancer patients.

A national research initiative, EPIC, will propel Canada to the forefront on cancer immunotherapy research. Building on prior investments in pre-clinical research, our proposal addresses the critical need for infrastructure to support immunotherapy research in the clinical setting. We will create three complementary, closely integrated research facilities:

1) Target Discovery and Vector Development: a state-of-the art facility that will use genomic and proteomic strategies to discover new molecular targets (antigens) for ACT and create novel strategies and tools for T cell engineering;

2) T Cell Engineering and Expansion: a cutting edge cell processing facility that will develop and implement innovative, cost-effective methods to generate safe and effective T cell products for use in clinical trials research; and

3) Immune Monitoring: a multi-platform suite for detailed profiling of immune responses in patients receiving new immunotherapies.

The goals of the EPIC initiative are to achieve rapid, cost effective implementation, increase the number of cancers that can be treated by ACT and enhancing the potency of ACT against solid tumours. EPIC will provide a complete developmental pipeline for these innovations that extends from lab-based research through to rigorous, first-in-human clinical trials, with the long-term goal of translating these concepts into standard of care for patients.