Section 4.4: CSC-directed immunotherapy (from DOI: 10.1038/s41392-020-0110-5)

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Article	Targeting cancer stem cell pathways for cancer therapy (DOI: 10.1038/s41392-020-0110-5)
Sections in this Publication
Section	Section 1: Introduction (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 2: The concept of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 2.1: Biological characteristics of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 2.2: Isolation and identification of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3: Factors regulating CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.1: Major transcription factors in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2: Major signaling pathways in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.1: Wnt signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.2: Notch signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.3: Hh signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.4: NF-kappaB signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.5: JAK-STAT signaling pathway (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.6: TGF/SMAD signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.7PI3K/AKT/mTOR signaling pathway in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.8: PPAR signaling pathways in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.2.9: Interactions between signaling pathways in CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3: The microenvironment of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.1: Vascular niche microenvironments and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.2: The hypoxia microenvironment and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.3: Tumor-associated macrophages and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.4: Cancer-associated fibroblasts and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.5: Cancer-associated MSCs and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.6: Extracellular matrix and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 3.3.7: Exosomes in the TME and CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4: Therapeutic targeting of CSCs (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.1: Agents targeting CSC-associated surface biomarkers in clinical trials (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.2: Agents targeting CSC-associated signaling pathways in clinical trials (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.3: Targeting the CSC microenvironment (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 4.4: CSC-directed immunotherapy (from DOI: 10.1038/s41392-020-0110-5)
Section	Section 5: Conclusions and perspectives (from DOI: 10.1038/s41392-020-0110-5)
Section	Competing interests (from DOI: 10.1038/s41392-020-0110-5)
Section	Bibliography (from DOI: 10.1038/s41392-020-0110-5)
Named Entities in this Section

From publication: "Targeting cancer stem cell pathways for cancer therapy" published as Signal Transduct Target Ther; 2020 ; 5 8; DOI: https://doi.org/10.1038/s41392-020-0110-5

Section 4.4: CSC-directed immunotherapy

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Table 4 data: Trial description Condition Sample size Phase NCT Number Current status CD19 CAR-T B cell leukemia and lymphoma II 80 NCT03398967 Recruiting CD123 CAR-T CD122+ myeloid malignancies II 45 NCT02937103 Recruiting CD22 CAR-T Recurrent or refractory B cell malignancy I/II 45 NCT02794961 Unknown CD22 CAR-T B-ALL I 15 NCT02650414 Recruiting CD33 CAR-T Myeloid malignancies I/II 45 NCT02958397 Recruiting CD33 CAR-T CD32+ acute myeloid leukemia I 11 NCT03126864 Active, not recruiting CD38 CAR-T B-ALL II 80 NCT03754764 Recruiting CD138 CAR-T Multiple myeloma II 10 NCT03196414 Recruiting MUC1 CAR-T/PD-1 KO Advanced esophageal cancer I/II 20 NCT03706326 Recruiting EGFR IL-12 CAR-T Metastatic colorectal cancer I 20 NCT03542799 Not yet recruiting MESO CAR-T Refractory-relapsed ovarian cancer I/II 20 NCT03916679 Recruiting MESO-19 CAR-T Metastatic pancreatic cancer I 4 NCT02465983 Completed LeY CAR-T Myeloid malignancies I/II 445 NCT02958384 Recruiting MOv19-BBz CAR -T Recurrent high-grade serous ovarian cancer I 18 NCT03585764 Recruiting LeY CAR-T Advanced cancer I 30 NCT03851146 Recruiting EpCAM CAR-T Recurrent breast cancer I 30 NCT02915445 Recruiting BCMA CAR-T Multiple myeloma II 80 NCT03767751 Recruiting

Table 4 caption: CSC-directed immunotherapy in ongoing clinical trials

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In the early twentieth century, Paul Ehrlich first proposed the idea that an intact immune system suppresses tumor development (advancing cancer therapy with present and Emerging Immuno-Oncology Approaches). Based on the understanding of cellular immune regulation, new methods for cancer treatment have emerged. In addition to the antibodies against the CSC molecules mentioned above, some novel anti-CSC immunotherapeutic approaches, such as immunologic checkpoint blocking or CAR-T cell therapies, have been developed. Some drugs that target the immune checkpoint receptors CTLA-4, PD-1 (nivolumab, pembrolizumab, and cemiplimab,) and PD-L1 (avelumab, durvalumab, and atezolizumab) have also been in clinical trials. I ipilimumab, a CTLA-4 antibody, is approved by the FDA, and initial clinical results showed good effectiveness in patients with metastatic melanoma. For CAR-T cell therapy, as shown in Table 4, CD19, CD20, CD22, CD123, EpCAM, and ALDH have been used for CSC-directed immunotherapy, and most of them are recruited.