Researchers at the University of California, Los Angeles (UCLA) Health Sciences have engineered a type of potent immune cell, called gamma delta T cell, that might be used as an “off-the-shelf” therapy for patients with ovarian and other difficult-to-treat cancers.
Also known as allogeneic therapy, “off-the-shelf” therapy uses immune cells taken from healthy donors rather than from patients. Currently, cell therapies like chimeric antigen receptor (CAR) T cell therapy are individualized for each patient by taking immune cells from their blood and engineering them to treat the patient’s specific cancer.
This process is expensive and time-consuming. However, as CAR T cell therapy is often applied in patients with advanced cancers, timeliness is essential. Researchers are therefore working on developing “off-the-shelf” therapies that can be produced at a large scale, are less costly, and would be readily available in clinics when needed.
In the study published in Nature Communications, the researchers focused on gamma delta T cells, which are known to have a good safety profile and can target many different cancers. However, the success of past clinical studies on gamma delta T cells has been limited due to “donor variability, short-lived persistence, and tumor immune evasion,” the researchers wrote in their paper.
To address these challenges, the research team took a closer look at gamma delta T cells. They found that cells with a higher expression of a protein called CD16 on their surface had a greater capability to target and kill cancer cells.
“These CD16-high gamma delta T cells exhibit unique characteristics that increase their ability to recognize a tumor,” explained Lili Yang, PhD, an associate professor at UCLA and a researcher on the study, in a press release.
The researchers used CD16 as a biomarker to select more potent T cells from donors. They then engineered the cells to equip them with CAR and IL-15, a protein responsible for immune responses. Both CAR and IL-15 can improve the anticancer-fighting abilities of gamma delta T cells.
In a preclinical study, the team produced high quantities of these newly engineered CD16 gamma delta T cells and tested them in two ovarian cancer models. The cells exhibited a high effectiveness and safety profile. Moreover, the cells were able to use different mechanisms to target and kill tumors, making them a viable future option for “off-the-shelf” cancer therapies.
“The results of this research shed light on the promising feasibility, therapeutic potential, and remarkable safety profile of these engineered CD16-high gamma delta T cells,” Yang said. “We hope this can be a viable therapeutic option for cancer treatment in the future.”
In their discussion, the researchers wrote that more work is needed, especially in the area of solid tumors. Current CAR T cell therapies on the market target liquid tumors, but solid tumors have a dense microenvironment, which makes them more difficult to reach. Hence, the researchers suggest studying the penetration efficiency of engineered CD16 gamma delta T cells in the future.
“Given the heterogeneity of solid tumors and their complex immunosuppressive tumor microenvironment, a multi-faceted approach to tumor recognition and immunomodulation will likely be necessary to achieve long-lasting therapeutic results in treatment-resistant patients,” concluded the authors.