The researchers and clinicians at Fox Chase Cancer Center have taken another important step forward on their journey to deliver truly personalized care to their patients with cancer. Members of the Department of Hematology/Oncology are partnering with their colleagues in the Department of Bone Marrow Transplant and Cellular Therapies to test the potential of adoptive cell therapies for the treatment of solid tumors.
Adoptive cell therapy is a form of immunotherapy in which a patient’s own immune system is harnessed in an attempt to recognize and destroy their cancer. Adoptive cell therapy includes chimeric antigen receptor (CAR) T-cell therapy—taking T-cells from the patient, genetically engineering them, expanding them, and re-implanting them. It also involves tumor-infiltrating lymphocyte (TIL) therapy—antitumor white blood cells found in a patient’s tumor. These “smart” white bloods cells are taken from the tumor, stimulated and grown in large numbers outside of a patient, and then given back to the same patient.
“In the treatment of hematologic malignancies, we have taken a big step forward in understanding how we can manipulate a patient’s immune system through T-cell receptors in an effort to capitalize on training the immune system on what to attack,” explained Anthony J. Olszanski, MD, RPh, vice chair of Clinical Research and associate professor, Department of Hematology/Oncology.
There are currently four CAR T-cell therapies approved for different hematologic malignancies.
“These treatments are designed in an effort to maximize efficacy and minimize toxicity,” Olszanski said. “Now, we want to bring that to solid tumors.”
Solid tumors, however, present a much larger challenge due to the heterogeneity within even a group of similar solid tumors. For example, the umbrella term “lung cancer” includes many forms of lung cancers with many different approaches to treatment.
“The promise of adoptive cellular therapy is in discovering therapies specifically for that patient and their tumor,” Olszanski said.
What Is Being Tested
Fox Chase is currently testing the potential of adoptive cellular therapy in a pilot study of patients with a specific type of non-small-cell lung cancer (NSCLC). The study will test adoptively transferred T-cells directed against New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens, two tumor-associated proteins found in several tumor types including NSCLC and sarcoma (NCT03709706).
Eligible patients must have a disease that meets the predefined threshold for expression of NY-ESO-1 and/or LAGE-1a. The trial is being led at Fox Chase by Martin J. Edelman, MD, chair and professor, Department of Hematology/Oncology.
“This is not a first-line treatment. We will screen patients diagnosed with stage IV NSCLC who may be eligible for the trial in the future,” Edelman explained. “Patients are HLA-typed and screened for expression of NY-ESO-1. If those criteria are met, we harvest the cells for the patient.”
Edelman explained that these cells will not be used right away, but instead are stored until the patient has disease progression. When needed, the genetically modified T cells, which target NY-ESO-1/LAGE-1, will be transferred back to the patient.
These genetically modified T cells are also being tested in patients with NY-ESO-1 positive sarcomas, said Margaret von Mehren, MD, vice chair and professor, Department of Hematology/Oncology.
“Sarcomas are rare in the United States, with about 15,000 diagnosed each year,” von Mehren said. “When you look at the specific types, there are probably 500 patients a year, at most, with this type.”
However, if patients with this subtype are not cured with initial surgery and other available therapies, this offers an approach that could potentially offer longer disease control.
“That is always the hope with cellular therapies, that it allows the immune system to be taught,” von Mehren said.
Administration of these new adoptive cellular therapies has required a new partnership between the solid tumor oncologists and their colleagues in bone marrow transplantation.
“If a patient is screened and HLA typing and antigen expression are correct, then we begin the interaction with the transplantation team,” Edelman said. “We partner with research nurses and coordinators to schedule the harvest of the cells. They are processed and stored, awaiting the potential day they are needed.”
Without a bone marrow transplant program, an institution could not provide adoptive cellular therapies as options for their patients, explained Henry Chi Hang Fung, MD, FACP, FRCPE, chair of the Department of Bone Marrow Transplant and Cellular Therapies at Fox Chase.
“This is a new option that has not existed for solid tumors in the past,” Fung said. “This is cutting-edge technology that is even more complicated than stem cell transplant. The Department of Bone Marrow Transplant and Cellular Therapies provides the infrastructure to make this happen.”
According to Edelman, the department of bone marrow transplant takes the wheel for facilitating the fairly complicated process to coordinate with the trial sponsor, arrange the dates for a patient to undergo conditioning and harvesting of cells, and then later infusion and monitoring.
“This has all been handled by the respective team in the Fox Chase Office of Clinical Research and has been done quite well,” he said.
Hope for the Future
It is still too early to tell whether these new treatment strategies will yield the success in solid tumors that has been seen in hematologic malignancies, but hopes are high.
In the future, Olszanski hopes to see adoptive cell therapy used in a plethora of clinical trials to attack solid tumors from a number of angles.
“We are really only at the tip of the iceberg when it comes to using adoptive cell therapy to attack the problem of malignancy,” Olszanski said.
“Right now, we are seeing a number of trials looking at certain subsets of cancer and trying to learn as much as we can about the interaction of the immune system with that malignancy,” he said. “In the future, we are going to see even more personalized cancer care where we take a patient’s tumor out of their system and very carefully educate their immune system to attack their tumor and repurpose their immune system to do the job.”