A combination of polypeptides for conditional regulation of an immune cell, the polypeptides comprising: (a) a chimeric transmembrane receptor polypeptide comprising (i) an extracellular region comprising an antigen interacting domain that binds an antigen and (ii) an intracellular region comprising an immune cell signaling domain; (b) a chimeric adaptor polypeptide comprising a receptor binding moiety that binds the receptor polypeptide when the receptor polypeptide has undergone a receptor modification upon binding to the antigen; (c) a gene modulating polypeptide comprising an actuator moiety linked to a cleavage recognition site, wherein upon release from the GMP the actuator moiety is capable of regulating gene expression and/or activity of a target polynucleotide; and (d) a cleavage moiety that cleaves the cleavage recognition site when in proximity to the cleavage recognition site to release the actuator moiety from the GMP; wherein in response to antigen binding the receptor is modified and the chimeric adaptor polypeptide is recruited to the receptor; wherein: (i) the cleavage moiety forms a portion of the intracellular region of the receptor polypeptide, and the GMP forms a portion of the chimeric adaptor polypeptide, wherein binding of the chimeric adaptor polypeptide to the receptor brings the cleavage moiety in proximity to the cleavage recognition site and wherein the cleavage moiety cleaves the cleavage recognition site to release the actuator moiety from the GMP; (ii) the cleavage moiety is complexed with a second adaptor polypeptide that binds the receptor polypeptide that has undergone the receptor modification upon binding to an antigen, and the GMP forms a portion of the chimeric adaptor polypeptide, wherein binding of the chimeric adaptor polypeptide and also the second adaptor polypeptide to the receptor brings the cleavage moiety in proximity to the cleavage recognition site and wherein the cleavage moiety cleaves the cleavage recognition site to release the actuator moiety from the GMP; or (iii) the cleavage moiety forms a portion of the chimeric adaptor polypeptide, and the GMP forms a portion of the intracellular region of the receptor polypeptide, wherein binding of the chimeric adaptor polypeptide to the receptor brings the cleavage moiety in proximity to the cleavage recognition site and wherein the cleavage moiety cleaves the cleavage recognition site to release the actuator moiety from the GMP (a) a chimeric transmembrane receptor polypeptide comprising (i) an extracellular region comprising an antigen interacting domain that binds an antigen and (ii) an intracellular region comprising an immune cell signaling domain; (b) a chimeric adaptor polypeptide comprising a receptor binding moiety that binds the receptor polypeptide when the receptor polypeptide has undergone a receptor modification upon binding to the antigen; (c) a gene modulating polypeptide comprising an actuator moiety linked to a cleavage recognition site, wherein upon release from the GMP the actuator moiety is capable of regulating gene expression and/or activity of a target polynucleotide; and (d) a cleavage moiety that cleaves the cleavage recognition site when in proximity to the cleavage recognition site to release the actuator moiety from the GMP; (i) the cleavage moiety forms a portion of the intracellular region of the receptor polypeptide, and the GMP forms a portion of the chimeric adaptor polypeptide, wherein binding of the chimeric adaptor polypeptide to the receptor brings the cleavage moiety in proximity to the cleavage recognition site and wherein the cleavage moiety cleaves the cleavage recognition site to release the actuator moiety from the GMP; (ii) the cleavage moiety is complexed with a second adaptor polypeptide that binds the receptor polypeptide that has undergone the receptor modification upon binding to an antigen, and the GMP forms a portion of the chimeric adaptor polypeptide, wherein binding of the chimeric adaptor polypeptide and also the second adaptor polypeptide to the receptor brings the cleavage moiety in proximity to the cleavage recognition site and wherein the cleavage moiety cleaves the cleavage recognition site to release the actuator moiety from the GMP; or (iii) the cleavage moiety forms a portion of the chimeric adaptor polypeptide, and the GMP forms a portion of the intracellular region of the receptor polypeptide, wherein binding of the chimeric adaptor polypeptide to the receptor brings the cleavage moiety in proximity to the cleavage recognition site and wherein the cleavage moiety cleaves the cleavage recognition site to release the actuator moiety from the GMP