T Cell Mass Production for Immunotherapy Offers New Potential Against Solid Tumors
Cancer immunotherapy using T cells has proven to be effective against certain blood and skin cancers but is less effective in tumors like colorectal cancer, which is one of the most frequent cancers worldwide. One primary consideration with T cell immunotherapy is that it needs to be tailored to each patient individually through time- and cost-intensive, procedures. The procedures involve isolation of a patient’s own T cells, their expansion and genetic engineering to target the cells towards the patient’s cancer cells. This complex process that limits the widespread availability of such treatments. Consequently, an “off-the-shelf” T cell immunotherapy – one that can be universally used safely in any person – that is safe and effective in a wide range of cancer patients, including patients with solid cancers, is highly desirable.
Towards this goal, Takashi Aoi from Kobe University, Japan, and his team focus on a special type of T cells called gamma delta T cells, which can potentially be used universally across a variety of patients and cancers due to their unique features. The work was published today in Stem Cell Reports. Gamma delta T cells do not discriminate between “own” and “foreign,” meaning that they can be given to patients without the need for immune matching and without risking attaching a patient’s own healthy cells. Additionally, rather than targeting one cancer-specific molecule at a time, gamma delta T cells target cancer cells based on “stress” signals, which are frequently sent out by cancer cells across the broad spectrum of cancer types. Based on this approach, gamma delta T cells are a potential source of immune cells for off the shelf cancer immune therapy. However, a limitation to the large-scale manufacturing of these cells is their low abundance in the blood together with their limited ability to multiply after isolation.
To overcome this bottleneck, Dr. Aoi’s team has come up with an upscaling method amenable to clinical grade production, by first converting isolated gamma delta T cells to immature stem cells, followed by their multiplication in the lab. Once this was done, the stem cells were turned back into T cells so that large quantities of gamma delta T cells could be obtained. Importantly, this procedure did not affect the T cells’ capability to target cancer cells. These lab-grown T cells proved to be highly effective against human patient-derived colorectal cancer cells, both in lab-based assays and in experimental animals, reducing cancer cell growth by 70-100%. At the same time, the T cells did not attack normal healthy cells even if there was an immunological mismatch.
This study provides a foundation for developing off-the-shelf T cell immunotherapies for solid tumors including colorectal cancer. Follow-up investigations on the efficacy and safety of this approach in a clinical setting will be required.
About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Stem Cell Reports is a Cell Press partner journal. Find the journal on X: @StemCellReports.
About ISSCR
Across more than 80 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to advancing stem cell research and its translation to medicine.