Targeted control of cell-based therapeutics

(Secret passageway)

With the development of cell-based therapies (e.g. stem cell therapies, CAR T cell therapies), the need to control their activation, differentiation, inhibition, proliferation, and survival after their infusion into patients has become important to their clinical success. To solve this problem, we have developed a "secret passageway" that can be inserted into any therapeutic cell type and exploited to mediate uptake of any desired drug into that therapeutic cell after its infusion into the patient. This secret passageway allows, for example, for delicate control of the differentiation program of a stem cell or sensitive modulation of CAR T cell activity after infusion into a patient. Because the targeted drug can be constructed to prevent its entry into any cell lacking the "secret  passageway", virtually all off-target toxicity can be prevented. Although animal studies have provided a compelling proof of concept, further work must still be performed to identify the most important applications of this new technology for adoptive cell therapies.