The Second International Cancer Immunotherapy Conference (CICON16), themed Translating Science Into Survival, explored a wide range of immunotherapy strategies that are grounded in science and improving patients’ lives. We covered how vaccines use abnormal cancer antigens to enhance anti-tumor immune responses, how new checkpoint immunotherapies are offering hope for patients with previously resistant tumors, how the tumor environment itself and even the bacteria in our bodies influence the immune system’s ability to root out cancer, and the enhanced effectiveness of combining multiple therapies that target different aspects of cancer’s behavior.
While this significant progress is very encouraging, the work is nowhere near done. To quote Winston Churchill as many immunologists already have, immunotherapy appears to be at “the end of its beginning.” To wrap up CICON16, experts turned their attention toward emerging treatments and technologies that will enable the field to keep moving forward far into the future.
The final day began with Elizabeth Jaffee, M.D., the deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine and a member of CRI’s Scientific Advisory Council. Jaffee specializes in pancreatic cancer, which is notorious for non-immunogenic tumor environments that render it resistant to current checkpoint immunotherapies. Using a mouse model for naturally resistant cancer, she’s examining how to convert these “cold” tumors into “hot” tumors that stimulate an immune response. Although vaccines by themselves have proven largely ineffective at eliminating tumors, they can facilitate T cell infiltration into tumors, which is a prerequisite for successful immunotherapy. Due to this, she cautioned that vaccines shouldn’t be abandoned until they’re tested in combination with T cell-empowering checkpoint inhibitors.
One of these vaccines is GVAX, developed in part by Novartis’ Glenn Dranoff, M.D., who also serves on CRI’s Scientific Advisory Council and is a member of CRI’s Cancer Immunotherapy Consortium (CIC) Steering Committee. GVAX uses inactivated pancreatic cancer cells genetically modified to express an immune stimulating molecule called GM-CSF. In an ongoing clinical trial, GVAX combined with the bacterial vaccine CRS-207 didn’t produce encouraging results, but when the anti-PD-1 checkpoint inhibitor nivolumab was added to the regimen, responses were seen in patients with metastatic cancer. Interestingly, some of these responses took up to 6 months, again highlighting the complex and sometimes delayed effects of immunotherapy, which oncologists need to take into account when evaluating patient responses. To improve the effectiveness of vaccines, Jaffee also stressed the need for adaptive clinical trials that identify and then target the specific immune-suppressing signals acting in individual patients’ tumors.
Epigenetic regulation―in which cancer cells modify the structure of DNA to silence the expression of certain genes―is another area that must be addressed, according to Weiping Zou, M.D., Ph.D., of the University of Michigan School of Medicine. Many cancers use this to prevent production of molecules that stimulate anti-cancer immune responses, resulting in tumors devoid of immune cells. When these cancers are treated with drugs, such as azacytidine and GSK126, that prevent this epigenetic regulation, they restored production of these pro-immune molecules, which increased anti-cancer T cell recruitment and infiltration into tumors.
As CICON16 wound down, technologies that will enable us to enhance our understanding of the interactions between tumors and the immune system became the focus of discussion. By building upon our existing knowledge, scientists will be able to identify new insights and use them to develop improved treatment approaches. Matthew Krummel, Ph.D., of the University of San Francisco, who is a member of CRI’s clinical leadership team, highlighted an important new imaging tool that uses 2 photon microscopy to reconstruct the tumor environment in 4-D (3 dimensions of space + 1 of time). Seeing where all the cells are positioned relative to each other could reveal new relationships between the different cell populations. Associations between those positions and clinical outcomes could reveal new insights and suggest new strategies.
Finally, the California Institute of Technology’s James Heath, Ph.D., spoke about the development of “barcoded” antibodies that, when targeted with a special type of light, can be used to enable the identification of rare, potentially anti-cancer T cell subsets in patients’ blood. This method achieves higher accuracy and precision while requiring far fewer T cells than current methods. Since anti-tumor T cell populations in the blood are much less abundant than in the tumor, this method can help determine if a patient has pre-existing anti-cancer T cells, and also allows doctors to monitor patients during treatment, to see whether―and which of―these anti-cancer T cell populations are responding to treatment and growing in number.
When we, the Cancer Research Institute (CRI), decided to team up with the American Association of Cancer Research (AACR), the Association for Cancer Immunotherapy (CIMT), and the European Academy of Tumor Immunology (EATI) to host the International Cancer Immunotherapy Conference (CICON) for the first time last year, we knew that immunotherapy was on the rise and were thrilled with the intense demand that it’s generated lately. Between the success of the inaugural CICON and the many breakthroughs that have happened in the field since then, we decided to host CICON again this year. Given the attention that this year’s meeting has received, I think that decision was more than validated.
While there were far too many exciting results from CICON16 to share all of them with you, we hope that our coverage has given you a well-rounded perspective on the current state of cancer immunotherapy, as well as the promising direction in which the field is heading. Cancer is still a dangerous foe, but if progress continues like this, there is hope that it may not always be so.