Rapamycin-activated cytokine receptor (RACR) (RACR)

The Rapamycin-activated cytokine receptor (RACR) is a synthetic, engineered receptor platform designed to provide precise control over the proliferation, survival, and differentiation of therapeutic immune cells, such as CAR-T cells and iPSC-derived cytotoxic innate lymphoid cells (iCILs) [2, 3]. Developed primarily for use in "off-the-shelf" and in vivo cell therapies, the RACR system utilizes the small molecule rapamycin (sirolimus) as a chemical inducer of dimerization [7, 9]. When rapamycin binds to the receptor's components, it triggers intracellular signaling pathways—specifically the JAK/STAT5 pathway—that mimic the effects of natural cytokines like IL-2 and IL-15 [5, 6]. This allows clinicians to selectively expand and maintain the engineered cell population in the patient without the need for toxic lymphodepleting chemotherapy or systemic cytokine administration [1, 11]. Furthermore, the use of rapamycin provides a dual benefit by simultaneously suppressing the host's immune response against the allogeneic therapeutic cells while driving their expansion through the RACR system [10, 12]. This technology is currently being evaluated in clinical trials for B-cell malignancies and has potential applications in solid tumors and autoimmune diseases [8, 13].

Other names

RACR systemRapamycin-inducible cytokine receptorSynthetic cytokine receptorRACR platform

The RACR system utilizes chemically induced dimerization (CID) where rapamycin acts as a molecular bridge to assemble synthetic receptor subunits, thereby initiating intracellular JAK/STAT5 signaling that mimics natural IL-2 and IL-15 cytokine pathways [2, 5, 6].