User login
Three of 6 patients treated had a response, including one that lasted more than five years. TILs were expanded ex vivo, and patients treated with lymphodepleting chemotherapy before the infusion, along with the checkpoint inhibitor pembrolizumab (Keytruda, Merck).
The results pave the way for recruitment of more patients as researchers at the National Cancer Institute ramp up the experimental treatment. They also help to overturn the long-held dogma that breast cancer is not immunogenic, according to lead researcher Steven A. Rosenberg, MD, PhD, who is chief of the surgery branch of the National Cancer Institute.
Although common hormone positive breast cancer doesn’t respond to immunotherapy, the study found that two-thirds of patients with metastatic breast cancer have mutations recognized by TILs. “We can identify the antigens [that] T cells recognize,” said Dr. Rosenberg, who is the lead author on a paper describing the pilot study, published online Feb. 1 in the Journal of Clinical Oncology.
There has been wide speculation that some solid tumors, including common hormone-positive breast cancers, are not immunogenic, because they don’t respond to cancer vaccines or checkpoint inhibitors. However, newer research has unearthed an explanation: Patients with these solid tumors produce immunogenic antigens, but they differ from patient to patient. There was not a single shared antigen among the 42 patients in the study. “Every patient reacts with a unique antigen, so the treatments have to be highly personalized,” said Dr. Rosenberg.
In the phase 2 study, the researchers recruited 42 participants, who underwent screening for novel tumor antigens. Sixty percent were hormone-receptor positive and HER2 negative, 26% were triple negative, and 14% were HER2 enriched.
Of 42 patients, 28 (67%) had at least one detectable, immunogenic tumor antigen, including 46% of HR+/Her2– patients, 32% of triple-negative patients, and 21% of HER2-enriched patients. Thirteen patients had a positive TIL screen, making them candidates for treatment.
Six patients underwent the procedure. Researchers selected TIL culture fragments that responded when stimulated with mutant peptides. They expanded those cells externally over 24 days and then administered lymphodepleting chemotherapy 1 week before the infusion of the expanded TILs. Patients received aldesleukin (Proleukin, Prometheus Laboratories) every 8 hours after TIL infusion, as tolerated. Patients also received pembrolizumab 2 days before the TIL infusion and up to three more doses at 3-week intervals.
Three patients experienced objective tumor regression, including a complete response that has lasted for 5.5 years. Two had partial responses that lasted 6 and 10 months. One patient with a partial response had a limited recurrence that could be excised, followed by further regression of other lesions, and was disease free 2 years after treatment.
The National Cancer Institute has just constructed a new building on the National Institutes of Health campus to pursue this research, and Dr. Rosenberg is actively recruiting patients to further study the treatment protocol. “We’re prepared to start treating large numbers of breast cancer patients with this. It’s highly experimental, it needs to be improved, it’s not ready for primetime. But we have now a signal that it can work,” said Dr. Rosenberg.
The study was funded by the National Cancer Institute. Dr. Rosenberg has received research funding from Kite, Iovance Biotherapeutics, and ZIOPHARM Oncology.
Three of 6 patients treated had a response, including one that lasted more than five years. TILs were expanded ex vivo, and patients treated with lymphodepleting chemotherapy before the infusion, along with the checkpoint inhibitor pembrolizumab (Keytruda, Merck).
The results pave the way for recruitment of more patients as researchers at the National Cancer Institute ramp up the experimental treatment. They also help to overturn the long-held dogma that breast cancer is not immunogenic, according to lead researcher Steven A. Rosenberg, MD, PhD, who is chief of the surgery branch of the National Cancer Institute.
Although common hormone positive breast cancer doesn’t respond to immunotherapy, the study found that two-thirds of patients with metastatic breast cancer have mutations recognized by TILs. “We can identify the antigens [that] T cells recognize,” said Dr. Rosenberg, who is the lead author on a paper describing the pilot study, published online Feb. 1 in the Journal of Clinical Oncology.
There has been wide speculation that some solid tumors, including common hormone-positive breast cancers, are not immunogenic, because they don’t respond to cancer vaccines or checkpoint inhibitors. However, newer research has unearthed an explanation: Patients with these solid tumors produce immunogenic antigens, but they differ from patient to patient. There was not a single shared antigen among the 42 patients in the study. “Every patient reacts with a unique antigen, so the treatments have to be highly personalized,” said Dr. Rosenberg.
In the phase 2 study, the researchers recruited 42 participants, who underwent screening for novel tumor antigens. Sixty percent were hormone-receptor positive and HER2 negative, 26% were triple negative, and 14% were HER2 enriched.
Of 42 patients, 28 (67%) had at least one detectable, immunogenic tumor antigen, including 46% of HR+/Her2– patients, 32% of triple-negative patients, and 21% of HER2-enriched patients. Thirteen patients had a positive TIL screen, making them candidates for treatment.
Six patients underwent the procedure. Researchers selected TIL culture fragments that responded when stimulated with mutant peptides. They expanded those cells externally over 24 days and then administered lymphodepleting chemotherapy 1 week before the infusion of the expanded TILs. Patients received aldesleukin (Proleukin, Prometheus Laboratories) every 8 hours after TIL infusion, as tolerated. Patients also received pembrolizumab 2 days before the TIL infusion and up to three more doses at 3-week intervals.
Three patients experienced objective tumor regression, including a complete response that has lasted for 5.5 years. Two had partial responses that lasted 6 and 10 months. One patient with a partial response had a limited recurrence that could be excised, followed by further regression of other lesions, and was disease free 2 years after treatment.
The National Cancer Institute has just constructed a new building on the National Institutes of Health campus to pursue this research, and Dr. Rosenberg is actively recruiting patients to further study the treatment protocol. “We’re prepared to start treating large numbers of breast cancer patients with this. It’s highly experimental, it needs to be improved, it’s not ready for primetime. But we have now a signal that it can work,” said Dr. Rosenberg.
The study was funded by the National Cancer Institute. Dr. Rosenberg has received research funding from Kite, Iovance Biotherapeutics, and ZIOPHARM Oncology.
Three of 6 patients treated had a response, including one that lasted more than five years. TILs were expanded ex vivo, and patients treated with lymphodepleting chemotherapy before the infusion, along with the checkpoint inhibitor pembrolizumab (Keytruda, Merck).
The results pave the way for recruitment of more patients as researchers at the National Cancer Institute ramp up the experimental treatment. They also help to overturn the long-held dogma that breast cancer is not immunogenic, according to lead researcher Steven A. Rosenberg, MD, PhD, who is chief of the surgery branch of the National Cancer Institute.
Although common hormone positive breast cancer doesn’t respond to immunotherapy, the study found that two-thirds of patients with metastatic breast cancer have mutations recognized by TILs. “We can identify the antigens [that] T cells recognize,” said Dr. Rosenberg, who is the lead author on a paper describing the pilot study, published online Feb. 1 in the Journal of Clinical Oncology.
There has been wide speculation that some solid tumors, including common hormone-positive breast cancers, are not immunogenic, because they don’t respond to cancer vaccines or checkpoint inhibitors. However, newer research has unearthed an explanation: Patients with these solid tumors produce immunogenic antigens, but they differ from patient to patient. There was not a single shared antigen among the 42 patients in the study. “Every patient reacts with a unique antigen, so the treatments have to be highly personalized,” said Dr. Rosenberg.
In the phase 2 study, the researchers recruited 42 participants, who underwent screening for novel tumor antigens. Sixty percent were hormone-receptor positive and HER2 negative, 26% were triple negative, and 14% were HER2 enriched.
Of 42 patients, 28 (67%) had at least one detectable, immunogenic tumor antigen, including 46% of HR+/Her2– patients, 32% of triple-negative patients, and 21% of HER2-enriched patients. Thirteen patients had a positive TIL screen, making them candidates for treatment.
Six patients underwent the procedure. Researchers selected TIL culture fragments that responded when stimulated with mutant peptides. They expanded those cells externally over 24 days and then administered lymphodepleting chemotherapy 1 week before the infusion of the expanded TILs. Patients received aldesleukin (Proleukin, Prometheus Laboratories) every 8 hours after TIL infusion, as tolerated. Patients also received pembrolizumab 2 days before the TIL infusion and up to three more doses at 3-week intervals.
Three patients experienced objective tumor regression, including a complete response that has lasted for 5.5 years. Two had partial responses that lasted 6 and 10 months. One patient with a partial response had a limited recurrence that could be excised, followed by further regression of other lesions, and was disease free 2 years after treatment.
The National Cancer Institute has just constructed a new building on the National Institutes of Health campus to pursue this research, and Dr. Rosenberg is actively recruiting patients to further study the treatment protocol. “We’re prepared to start treating large numbers of breast cancer patients with this. It’s highly experimental, it needs to be improved, it’s not ready for primetime. But we have now a signal that it can work,” said Dr. Rosenberg.
The study was funded by the National Cancer Institute. Dr. Rosenberg has received research funding from Kite, Iovance Biotherapeutics, and ZIOPHARM Oncology.
FROM JOURNAL OF CLINICAL ONCOLOGY