The present application relates to a chimeric antigen receptor (CAR) which comprises a target-dependent on-switch CAR. The CAR of the invention may reduce cytotoxicity towards normal cells and improve CAR-T safety. CAR molecules were designed using the transmembrane and juxtamembrane motifs of the IL2 receptor β chain (IL2Rβ or IL2Rb), the L ow-Density Lipoprotein Receptor (LDLR), the Seizure 6-like Protein 2 (SEZ6L2), and degradation sequence (PSKFFSQL) of IL2Rβ, which resulted in greatly reduced CAR expression at the cell surface in the absence of target antigen, while retaining downstream activation ability in response to antigen-expressing target cells. In the absence of target antigen, CAR surface expression is undetectable. The present application has shown that primary T cells expressing these surface-unstable CAR variants are able to elicit antigen-dependent target cell killing. By limiting CAR activity in this way, the present application can reduce therapeutic toxicity and T cell exhaustion. Due to its limited detectability in the absence of antigen, the present application refers to this system as a “Stealth CAR”. The present application further relates to compositions, preparation methods and uses of the Stealth CAR of the present application.

Provided herein are compositions including compounds and/or cells for treating a disease associated with Group 2 innate lymphoid cells (ILC2s), and methods of treatment.

Chlorotoxin derivatives containing amino acid sequence

TABLE-US-00001 X.sub.0X.sub.1CMPCX.sub.S1X.sub.S2X.sub.S3DHX.sub.S4X.sub.S5ARRCX.sub.2X.sub.3CCGGYGX.sub.4CFGYQC LCX.sub.5X.sub.6X.sub.7X.sub.8
wherein (i) the N-terminal X.sub.0X.sub.1 cluster is AM, 0M, or 00; (ii) the solubility X.sub.S1X.sub.S2X.sub.S3X.sub.S4X.sub.S5 cluster is FTTQT, FTTES, SSSQT, SSSES, FSSQT, FSSES, or FSSQS; (iii) the internal X.sub.2X.sub.3X.sub.4 cluster is DKR, RDK, KDR, IKY, HKW, DRK, LKQ, KKK; and (iv) the C-terminal X.sub.5X.sub.6X.sub.7X.sub.8 cluster is N000, R000, NR00, NRG0, NRGY, NRRR, or RRRR;
0 denotes a position where no amino acid is present; the chlorotoxin derivative has a relative human MMP-2 binding that is at least 1.62 times higher than the wild-type chlorotoxin of SEQ ID NO: 1. Conjugates containing the chlorotoxin derivatives and a method for preparing then, theranostic pairs containing the conjugates, kits containing the conjugates or the theranostic pairs, pharmaceutical compositions containing the conjugates, methods of treating cancer, nucleic acid molecules encoding a chimeric antigen receptor which contains the chlorotoxin derivative and vectors containing the nucleic acid.