In a report on what is believed to be the first small clinical trial of its kind, researchers at the Johns Hopkins Kimmel Cancer Center say they have safely used immune cells grown from patients’ own bone marrow to treat multiple myeloma, a cancer of white blood cells.
Experts report there are more than 20,000 new cases of multiple myeloma and more than 10,000 deaths each year in United States. It is the second most common cancer originating in the blood.
The current study involved a particular type of tumour-targeting T cell, known as marrow-infiltrating lymphocytes (MILs). The data findings showed that large numbers of activated MILs can selectively target and kill myeloma cells. The team explain that MILs are the foot soldiers of the immune system and attack foreign cells, such as bacteria or viruses. However, in their normal state, they are inactive and too few in number to have a measurable effect on cancer. Previous studies by the team showed that activated MILs could selectively target and kill myeloma cells taken from patients and grown in laboratory culture flasks.
For the current study the team enrolled 25 patients with newly diagnosed or relapsed multiple myeloma, although three of the patients relapsed before they could receive the MILs therapy.
The researchers retrieved MILs from each patient’s bone marrow, grew them in the laboratory to expand their numbers, activated them with microscopic beads coated with immune activating antibodies and intravenously injected each of the 22 patients with their own cells. Three days before the injections of expanded MILs, patients received high doses of chemotherapy and a stem cell transplant, standard treatments for multiple myeloma.
One year after receiving the MILs therapy, 13 of the 22 patients had at least a partial response to the therapy, meaning that their cancers had shrunk by at least 50 percent.
Seven patients experienced at least a 90 percent reduction in tumour cell volume and lived, on average, 25.1 months without cancer progression. The remaining 15 patients had an average of 11.8 progression-free months following MILs therapy. None of the participants had serious side effects from the MILs therapy. The overall survival was 31.5 months for those with less than 90 percent disease reduction, but this number has not yet been reached in those with better responses. The average follow-up time is currently more than six years.
The team note that several U.S. cancer centers have conducted similar experimental treatments, known as adoptive T cell therapy, however the researchers state that their study is believed to be the only one to use MILs. Other types of tumour-infiltrating cells can be used, but they are usually less plentiful in patients’ tumours and may not grow as well outside the body.
The team state that in nonblood-based tumours, such as melanoma, only about one-half of patients have T cells in their tumours that can be harvested, and only about one-half of those harvested cells can be grown. Typically, immune cells from solid tumours, called tumour-infiltrating lymphocytes, can be harvested and grown in only about 25 percent of patients who could potentially be eligible for the therapy. However, the researchers add that in their clinical trial, they were able to harvest and grow MILs from all 22 patients.
The results of the small trial helped the researchers learn more about which patients may benefit from MILs therapy. For example, they were able to determine how many of the MILs grown in the lab were specifically targeted to the patient’s tumour and whether they continued to target the tumour after being infused. Additionally, the team also found that patients whose bone marrow before treatment contained a high number of certain immune cells, known as central memory cells, also had better response to MILs therapy. Results showed that patients who began treatment with signs of an overactive immune response did not respond as well.
The team has used these data to guide two other ongoing MILs clinical trials. These new studies are trying to extend anti-tumour response and tumour specificity by combining the MILs transplant with a Johns Hopkins-developed cancer vaccine called GVAX and the myeloma drug lenalidomide, which stimulates T cell responses.
The researchers state the current study has also shed light on new ways to grow the MILs. Adding that in most of these trials the more cells produced, the better response you get in patients. Learning how to improve cell growth may therefore improve the therapy.
The team are now developing MILs to treat solid tumours such as lung, esophageal and gastric cancers, as well as the pediatric cancers neuroblastoma and Ewing’s sarcoma.