Fig. 4 |. Evaluation of GESP combinations for logic-gated CAR-T design.

a, Schematic illustration of the logic-gated ‘AND CAR-T’ design. b, The workflow to identify paired GESPs for ‘AND CAR-T’ design. c, Examples of identified caGESP pairs for ‘AND CAR-Ts’: MSLN-TM4SF4 for PAAD (left), and GPC3-TM4SF5 for liver hepatocellular carcinoma (right). Red text: the cancer type targeted by ‘AND CAR-T’, green text: the normal tissues in which the caGESP is expressed at low levels (that is, the tissue types with potential ‘on-target–off-tumor’ effects). Identified caGESP pairs are coexpressed in a select cancer type (red), and are mutually exclusively expressed in normal tissues (green). The horizontal line in the box plot indicates the median, and the whiskers indicate 1.5× IQR of the first and third quartiles. The sample size used to derive statistics is reported in Supplementary Tables 3 and 4. d, Number of the identified ‘AND CAR-T’ pairs for each cancer type. e, Schematic illustration of the iCAR-T design. f, The workflow to identify paired GESPs for iCAR-T design. g, Examples of identified caGESP–GESP pairs for iCAR-Ts: CA9-SLC26A9 for kidney renal clear cell carcinoma (left) and GPA33-TMIGD1 for chronic obstructive airway disease (right). Red text: the cancer type targeted by iCAR-T, green text: the normal tissues in which the caGESP is expressed at low levels (that is, the tissue types with potential ‘on-target–off-tumor’ effects). The identified caGESP–GESP pairs are mutually exclusively expressed in a select cancer type (red) and are coexpressed in normal tissues (green). The horizontal line in the box plot indicates the median, and the whiskers indicate 1.5× IQR of the first and third quartiles. The sample size used to derive statistics is reported in Supplementary Tables 3 and 4. h, Number of the identified iCAR-T pairs for each cancer type.