Scientists at ASCO16 revealed promising clinical trial results that could pave the way for new T-cell based immunotherapies for more cancer patients.
T cells are our most efficient cancer-killing cells in our body. As a result, many efforts have focused on improving their ability to root out cancer cells. Some immunotherapies provide signals to boost anti-tumor T cell activity while others actually supply T cells to patients. One technology, known as CAR T cells therapy (which we have covered here and here), genetically reprograms normal T cells to give them superior capabilities.
The CAR T successes in treating patients with leukemia and lymphoma are unprecedented, with response rates around 80-90%. Unfortunately, while blood cancer patients have benefited greatly, that success hasn’t yet translated to other cancer patients. One reason is that the B cells in many blood cancers are easier to target. B cells almost always express CD19 or CD22, while few other cells do. Therefore, CAR T cells designed to attack CD19 or CD22 (depending on a patient’s particular disease) can eliminate the malignant cells very effectively. Solid cancers have proven harder to treat because they rarely possess a marker, such as a CD19 or CD22, that’s not also shared by normal, healthy cells. Fortunately, new T cell strategies may be able to overcome this.
One of these strategies, which used CAR T cells to treat ovarian cancer patients, was presented by Janos Laszlo Tanyi, M.D., Ph.D. of the University of Pennsylvania Perelman School of Medicine and conducted in collaboration with Carl June, M.D., also of UPenn’s Perelman School as well as a member of both CRI’s Scientific Advisory Council and the leadership team of CRI’s clinical program. In their work, the team constructed CAR T cells designed to attack the mesothelin marker on ovarian tumors. While mesothelin is also on mesothelial cells, it’s often expressed at much higher levels on cancer cells, and provides a target for these CAR T cells. It’s still very early―only six patients were treated―but none of their tumors had progressed at Day 28. Promisingly, the anti-mesothelin CAR T cells also engrafted and expanded within patients, and even trafficked to multiple tumor sites. Also, no patients experienced “cytokine storm”―a potentially deadly condition sometimes resulting from CAR T treatments.
Another strategy took T cells and, rather than genetically modifying them, exposed them to cells infected by the Epstein-Barr virus (EBV). These EBV-primed T cells were then put into patients with nasopharyngeal carcinoma, a cancer commonly associated with EBV infection. Out of 14 patients treated, four patients experienced disease control and remain alive at 20.4–48.3 months post treatment. In addition to two partial responses, one patient achieved a complete response for more than a year and a half. Unlike the CAR T approach above, in which T cells were engineered to target a specific marker (mesothelin), this approach allows T cells to “learn” what to look for on their own by exposing them to other EBV-infected cells. Perhaps the most promising aspect of this approach is that these anti-EBV T cells don’t need to be patient-specific. Instead, this work showed that it’s possible to make and store universal stocks ahead of time, so that they’ll be readily available to treat more than 99% of patients.