Intro: The American Association for Cancer Research (AACR) publishes a forecast blog post at the start of each year to ask prominent cancer research leaders what they envision the new developments will be in areas like immunotherapy, precision medicine, cancer prevention, and health disparities.
|In this excerpt from the 2017 post in Cancer Research Catalyst, we interviewed immunotherapy expert Elizabeth Jaffee, MD, on her views on what might develop in immunotherapy this year. Dr. Jaffee is the Dana and Albert “Cubby” Broccoli Professor of Oncology and Professor of Pathology at Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. She is also the Associate Director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins. Dr. Jaffee was recently named the President-Elect of AACR for 2017-2018.|
Q: The American Association for Cancer Research (AACR) is arguably the World’s most important professional organization of volunteers in the cancer field. As we enter 2017, what does AACR consider the field’s greatest challenges and opportunities?
We have already turned this knowledge into therapeutics that inhibit some of these signals (checkpoint inhibitors) so the T cells can be effective in attacking the cancer cells, and developing therapeutics that can activate certain other cells within the tumor microenvironment (checkpoint agonists) to help further activate the T cells, she says.
With these approaches, we have been able to convert some metastatic cancer patients with weeks to live into those with chronic disease living a better quality of life, Jaffee adds. In 2017, we are going to see checkpoint inhibitors being approved for more cancer types and as first-line treatment for some cancers, she notes.
The bad news, however, is that these drugs only work for about 20 to 25 percent of all cancers. Further, these drugs can unleash autoimmunity in patients who respond. The side effects can be controlled currently with steroids in some patients, but this year we will learn more about ways to deliver these drugs in a more targeted way to circumvent the toxic side effects, Jaffee says.
“In 2017, I expect to see the development of new drugs that target additional immune checkpoints,” says Jaffee. One reason why almost 70 percent of cancers do not respond to checkpoint inhibitors is that the cancer cells inhibit different pathways that affect T-cell function. Therapeutics targeting immune-evasion mechanisms other than the PD-1/PD-L1 checkpoint, such as IDO, CD40, OX40, TIM-3, LAG-3, and KIR, are already in early clinical development. We will see them progress to clinical testing, alone or in combination with PD-1/PD-L1 drugs, and some of them may be approved or may come close to approval this year, Jaffee predicts.
This year, we will also see a lot of preliminary data identifying new biomarkers of immunotherapy response, according to Jaffee.
Other approaches to get more patients to respond to immunotherapies include activating T cells using vaccines, radiation therapy, or different types of immune-activating chemotherapies, Jaffee says. Combining immune checkpoint inhibitors with agents that can help uncover cancer antigens, such as PARP inhibitors that can make new tumor antigens available to the T cells, or epigenetic agents that can turn on the expression of certain proteins, is another avenue. “We will start seeing results from such studies this year,” Jaffee notes.
We are likely to make more progress this year in personalizing cancer treatment with vaccines, Jaffee predicts. “We are starting to understand the importance of neoantigens for targeting by the immune system,” Jaffee notes. Tumors of many patients who respond to immunotherapy create neoantigens constantly. If we can identify them by sequencing the tumors, we can develop vaccines against them to jump-start the immune system, she says. “We are going to see several clinical trials trying this approach this year.”
“As a member of the Blue Ribbon Panel, one of the 10 areas we identified as at the point of making huge progress is basic research to better understand the mechanisms behind immunotherapy response,” says Jaffee. Answers to questions such as, “What makes a pancreatic cancer that doesn’t respond to immunotherapy different from melanoma that responds to immunotherapy?” or “Why do some tumors that have the biomarker of response not respond while some that do not have the biomarker respond?” or “How to make CAR T-cell therapy work in solid tumors?” can only be found by pursuing more basic science research, she notes.
“We have the technology to find answers to many basic research questions and there is excitement among academia, industry, and federal agencies to work together; however, we need more funding to pursue such important studies,” says Jaffee. While she is concerned about the uncertainty regarding the scientific priorities of the new administration, she is cautiously optimistic.