Universal CAR-Ts (No. 1884)
Lead Researcher: Prof. Zelig Eshhar
Chimeric Antigen Receptor T-Cells (CAR-Ts) are one of the revolutionary technologies of the twenty-first century, invented by Prof. Zelig Eshhar at the Weizmann Institute of Science. The CAR-T technology represents a leap in terms of treating cancer, as the technology programs an individual’s immune system to specifically target and destroy malignancy.
However, the CAR-T technology still suffers from a number of shortfalls. These include the logistic complexity in terms of producing said CAR-Ts, issues of using a patient’s own immune cells – as the cancer in most cases has reduced both the number of T-Cells and their effectiveness, and overall labor intensiveness of the entire process. Consequently, there is a strong desire to shift away from autologous cells (a patient’s own cells) and to using allogeneic cells (donor cells) as the basis of CAR-Ts, to create a truly “off-the-shelf” treatment.
The group of Prof. Eshhar has developed a method for an adoptive cell therapy, such that cells from donors can be applied in a patient. The technology have already shown positive results in mouse models and Prof. Eshhar’s team is looking to translate the work into human subjects.
? A method for Universal CAR-Ts
? Simplifying the application of CAR-Ts
? Reduction of cost
? Possibly more effective CAR-T cells – using non-exhausted immune cells
The basis of the Universal CAR-T technology is that it uses a fundamental understanding of the immune system to allow for adoptive cell therapy. The Eshhar’s group protocol uses both controlled lympho-depletion and repurposes the FDA approved drug Fingolimod (Gilenya), which sequesters a patient’s lymphocytes to the lymphoid organs. These two actions permit allogenic T-Cells to effectively function unhindered by the innate immune system, creating an optimal therapeutic window for the CAR-Ts to destroy the malignancy. Additionally, the technology avoids the challenges of host versus graft response, due to blocking the egress of cells from the lymphoid organs. Present experimental work has shown it effective in mouse models.
The technology also has numerous advantages including a simplified production process for CAR-Ts, non-exhausted cells leading to a better outcomes, and a general flexibility as the technology could function regardless of target (e.g. not CD19 exclusive) or even cell type (e.g. could be applied for TCRs, or next generation CAR therapies such as CAR-Macrophages).