Cultivating and Administering Next-Generation Diagnostics and Treatments
Cancer ranks as the second leading cause of death in the United States, killing nearly as many people as heart disease. To combat this crisis, in July Mount Sinai launched the Center for Personalized Cancer Therapeutics (CPCT), within The Tisch Cancer Institute, where we are receiving the support necessary to elevate cancer therapy to a highly personalized level. Here is a brief overview of how our two labs are working to help cancer patients live longer while enjoying an improved quality of life.
The Cagan Lab: Mixing New Drug Cocktails
Our goal at CPCT is to move beyond the “one gene, one drug” philosophy of conventional drug design to cultivate novel cancer treatments that are based on a patient’s personal cancer genome. In the Cagan lab, we are exploring tailored drug cocktails that are best aligned to a patient’s tumor. Combinations of drugs have succeeded in treating HIV, and we expect cancer patients to benefit from a similar approach. Currently our investigations focus on triple negative breast cancer, head and neck cancer, and colon cancer, with plans to expand the number of cancers we treat.
With the help of the Institute for Genomics and Multiscale Biology and Minerva, its supercomputer, we are generating novel treatments. Minerva processes vast amounts of patient-specific data to produce precise mutational analysis and network analyses that describe the happenings within a patient’s tumor. With this information, we develop “personalized fruit flies” that match the details of a patient’s tumor. Robotics then screen thousands of drug combinations, and we use each patient’s fly line to develop a customized treatment for him or her.
The Bhardwaj Lab: Boosting a Patient’s Immune Response
Dedicated to advancing the understanding that immune control is critical to controlling cancer, we develop immune-based interventions, including antibody therapies and vaccines. To accelerate discovery in this arena, Mount Sinai is constructing a sophisticated vaccine facility featuring labs for viral and non-viral research, with air-lock rooms creating a controlled environment for the development of novel cell-based therapies and vaccines.
When the immune system becomes compromised in late-stage cancer, white cells (T cells) become “exhausted” and unable to kill tumor cells. Researchers have determined that blocking “checkpoints” associated with exhaustion can reverse immune suppression to improve response in several advanced cancers. We have since identified exhaustion markers on another type of white cell -Natural Killer cells – that promise to be similarly amenable to modulation.
Vaccinating Against Tumors
Our team identified a subgroup of dendritic cells often referred to as “sentinels of the immune system,” that are involved in the early detection and immune response to cancer. We were among the first to grow dendritic cells in the vaccine lab for patient trials and verify their immunogenicity against tumor and viral antigens in humans.
The first cell-based vaccine approved by the FDA, Sipuleucel-T, relied upon the inclusion of dendritic cells. We are now advancing this approach by developing vectors to insert genes into dendritic cells and enhance their immune-activating potential. Because they are based on the patient’s biologic material, these cells can be delivered in very high amounts to generate effective anti-tumor immunity.
We are also developing additional unique dendritic cell targeted and personalized approaches to boost immunity in patients with cancer. We are in early research, but we estimate these and other approaches will achieve greater than 50 percent response rates in melanoma and other cancers.
In addition, we are testing other vaccines with the potential for strong clinical impact, including oncolytic viruses that mobilize dendritic cells to treat melanoma, ovarian cancer, and cancers of the breast, head and neck, and a viral mimic that, when injected into the tumor, may be even more effective in controlling its growth.
Ross L. Cagan, PhD
Professor, Development and Regenerative Biology
Nina Bhardwaj, MD, PhD
Director, Cancer Immunology and Immunotherapy Program