Engineered T-cells Outfoxing Tumors

A research team has been able to validate a way to outsmart tumors. Engineered T-cells strip tumors of their self preservation skills and were able to hold Hodgkin lymphoma at bay in patients with relapsed disease for more than 4 years without requiring pretreatment chemotherapy as published in the Journal of Clinical Oncology.

T-cells actively seek out and destroy the proteins expressed by cancer cells or virus infected cells, thus protecting the body from infection and malignancy.  In this dose escalation study 8 patients with Epstein Barr virus positive Hodgkin lymphoma received between 2 and 12 doses between the amounts of 1.5 x 108 and 2 x 107 cells/m2 of T-cells which had been specifically engineered. The production of transforming growth factor in the immediate locations of tumors complicates tumor direct therapies by having harmful effects on T-cell function in vivo. To combat this issue researchers forced expression of a dominant negative TGF receptor type 2 onto LMP specific T-cells which were designed specially to seek out and destroy the proteins that are derived from Epstein Barr virus expression by the tumor cells. Dominant negative TGF receptor type 2 expressed by the T-cells gives the cells the ability to resist the hostile tumor environment and enables them to be able to seek out and destroy the tumor cells.

7 out of the 8 patients that were treated had active disease at the time of the T-cell infusion. 4 out of the 7 patients achieved clinical responses that were complete and ongoing, in 2 patients for more than 4 years, including 1 patient who had achieved only a partial response to unmodified tumor directed T-cells.

With the resistance to otherwise inhibitory concentrations in vitro the T-cells retain the ability to kill cancer cells. After infusion signals from the genetically modified T-cells in peripheral blood increased up to 100 times fold.

The team notes that their findings highlight the potential utilities of expressing LMP specific T-cells when combating other tumors that have learned to evade the immune system.