A Trial for Every Brain Tumor: Novel Approaches to Immunotherapy and Precision Medicine
Aug 27, 2021 Cedars-Sinai Staff
There is virtually no brain cancer that Jeremy Rudnick, MD, refuses to take on.
“Our goal is to have a trial open for every patient,” he said.
In his neuro-oncology practice and clinical research at Cedars-Sinai, Rudnick treats patients with aggressive brain tumors that cannot be treated with standard radiation, chemotherapy or surgical options. From breakthrough clinical trials of brain tumor vaccines to molecular targeted therapy, Rudnick’s patients benefit from the latest cutting-edge innovation.
“We have a lot of opportunities for patients to do things other than the standard of care,” he said. “For patients with certain tumors, we know the standard of care, and we want to raise the bar.”
"We have a lot of opportunities for patients to do things other than the standard of care. For patients with certain tumors, we know the standard of care, and we want to raise the bar.”
Rudnick and his team of physicians and researchers at Cedars-Sinai are recognized leaders in immunology, which harnesses the power of the patient’s own immune system.
“We know the immune system actually has the potential to kill cancer,” he said. Typically, however, a tumor is able to “cloak” itself so that it is unseen by the immune system, evading attack.
Rudnick and his team at Cedars-Sinai have developed therapies to either remove the tumor’s cloaking device or enhance the immune system so that the body is able to attack the tumor itself.
“We’re basically stepping on the gas pedal with our immune system and simultaneously braking on the tumor,” Rudnick said.
Immunotherapy can also be combined with traditional approaches, including radiation therapy.
To treat a single patient, the team may combine multiple immunotherapy approaches, including checkpoint inhibitors, dendritic cell vaccines and viral therapy.
“We use different combinations and permutations for each patient,” Rudnick said.
The “cloaking device” the tumor uses to evade the immune system is a checkpoint receptor, a cell protein that modulates immune response. Some tumors produce PD-1, a receptor that causes the tumor cell to appear as normal tissue to T-cells.
One type of immunotherapy introduces checkpoint inhibitors targeting PD-1 activity to remove a tumor’s ability to masquerade as normal tissue, allowing T-cells, B-cells or white blood cells to attack the tumor.
Dendritic Cell Vaccine Therapy
In a current active trial Rudnick is involved in, PD-1 and dendritic cell vaccines are applied together as combinatorial immunotherapy.
With dendritic cell vaccine therapy, the team takes tumor antigens either from a patient or off the shelf. Next, they isolate the patient’s white blood cells and expose them to the antigens. This process turns the patient’s white blood cells into antigen-presenting cells. The antigen-presenting cells are reintroduced back into the body, primed to attack and kill the tumor.
“You’re basically taking the patient’s immune cells and giving them the scent of what to go after,” Rudnick explained.
Rudnick is encouraged by the potential for the treatment. However, there’s still a lot to learn about how the therapy works.
“We still don’t know exactly how to harness the power of the immune system,” he said.
Rudnick led a dendritic cell vaccine trial at Cedars-Sinai in 2017 that was developed in the laboratory of John Yu, MD. Next, Rudnick will be initiating a T-cell therapy trial developed in Yu’s Lab, which is currently undergoing regulatory approvals.
“Of the original 30 patients, one-third survived for extended periods of time, over five years, and I still have some of those patients in my clinic today,” Rudnick said. “It’s unheard of. But, when we carried out larger Phase II and III trials, we didn’t see the same results.”
Another mechanism for immunotherapy involves introducing a virus into the tumor.
A surgeon injects a modified adenovirus directly into the tumor, transfecting the tumor. The immune system is then able to recognize the virus, and because the virus is attached to the tumor, attacks the tumor as well, creating cross-reactivity.
Molecular targeted therapy
In addition to immunotherapy, Rudnick researches targeted therapy, also referred to as molecular therapy or precision medicine.
With these methods, the team attempts to understand the immune response at the cell level, and then prime the cells to continue to adapt to respond to the cancer through cellular mutation. Sequencing both the patient’s immune cells and tumor cells can reveal how the two interact and predict how the tumor may react.
To stop the tumor from growing, the body must continually adapt as the tumor changes its course of attack.
“The immune system can evolve rapidly, the way a tumor can evolve,” Rudnick said.
In one current trial with the Brain Tumor Alliance, Rudnick and his team work with tumor types that have a TRK end track mutation. A commercially available drug responds to the mutation, shutting down the tumor’s pathways to communicate with the body.
The mutation can be found in various types of malignant tumors throughout the body. Whether the tumor is in the brain, breast, lungs or elsewhere does not impact its responsiveness to targeted therapy.
For example, Rudnick is principal investigator on a trial targeting the c-MET mutation found in both non-small cell lung cancers and glioblastomas.
“Even though I’m a neuro-oncologist, the c-MET mutations in both locations are treated with the same drug,” he said.
The future of individualized patient care
Cedars-Sinai is proud to provide truly customized cancer care.
“We sequence all of our patients, which isn’t something that’s always standard of care,” Rudnick said. “We know exactly what’s going on, and we pick trials we think would be most applicable for an individual patient.”
Cedars-Sinai currently has 10 active trials investigating a combination of immunotherapy methods and traditional treatment options available to patients with brain tumors. Patients with newly diagnosed tumors, including glioblastoma or recurring malignant tumors, including gliomas, pituitary tumors and brain metastases may be candidates.
Rudnick encourages physicians to refer patients to Cedars-Sinai and involves referring doctors as a close part of a patient’s care team.
“We really partner and continue to work with the referring physician,” Rudnick said. His research continues to push the boundaries of cancer care, looking for a cure for each of his patients.