Table 1. Selected immune checkpoint inhibitors in SCLC.
| Target | Expressing cells | Roles in cancer immunity | Agents | Class | Ongoing monotherapy studies |
|---|---|---|---|---|---|
| CTLA-4 | Tumor cells and T cells(activated/exhausted/Tregs) | Negatively regulates the early stage of naïve T cells activation by blocking costimulatory pathway | Ipilimumab | Fully human IgG1 antibody | – |
| Tremelimumab | Fully human IgG2 antibody | – | |||
| PD-1 | Tumor-infiltrating lymphocytes including T cells and B cells | Promote the exhaustion of CD8+ T cells and the differentiation of Tregs | Nivolumab | Fully human IgG4 antibody | NCT02481830 |
| Durvalumab | Humanized IgG1 antibody | NCT03043872 | |||
| Pembrolizumab | Humanized IgG4 antibody | NCT03526887 | |||
| NCT01840579 | |||||
| NCT02721732 | |||||
| NCT02628067 | |||||
| NCT02963090 | |||||
| PDR001 | – | ||||
| PD-L1 | Tumor cells, macrophages, myeloid DCs, MDSC, stromal fibroblasts, and endothelial cells | Atezolizumab | Fully human IgG1 antibody | NCT03782207 | |
| NCT03059667 | |||||
| Sintilimab | – | ||||
| Avelumab | – | ||||
| TIM-3 | T cells (including Tregs), macrophages, DCs, NK cells, and mast cells | Mediate T-cell exhaustion and suppress innate antitumor immunity | RO7121661(PD-1/TIM-3 bispecific antibody) | Bispesific antibody | NCT03708328 |
| INCAGN02390 | Fully human Fc-engineered IgG1κ antibody | NCT03652077 | |||
| LAG-3 | Tumor cells, T cells (including Tregs), B cells, NK cells, DCs, and TILs | Inhibit the activation of T cells and the differentiation of macrophages or fully competent antigen-presenting DCs | INCAGN02385 | Fc-engineered IgG1κ | NCT03538028 |
| XmAb®22841 | Bispesific antibody | NCT03849469 | |||
| LAG525 | Monoclonal antibody | NCT03365791 | |||
| OX40 | Endothelial cells, mast cells, activated NK cells, DCs, B cells, microglial cells, activated T cells and Foxp3+ Tregs | Enhance the differentiation of CD4 memory T cell, CD4+ T cells and Th2 cells and activate NK cells | INCAGN01949 | IgG1 monoclonal antibody | – |
| GITR | Expressed high levels on Tregs and at low levels on naïve and memory T cells | Promote NFκB activation, IL-9 production and cytotoxic T lymphocyte responses, enhance the function of DCs and Tregs expansion, and inhibits Tregs suppressive function | INCAGN01876 | – | – |
| IDO1 | Mature DCs, pulmonary and placental endothelial cells and tumor cells | Favor the growth of tumors, promote the differentiation of Tregs and induce inflammation-associated tumorigenesis | Epacadostat | – | – |
| TIGT | CD8+ TILs, Foxp3+ Tregs, monocytes, and NK cells | Inhibit activation of T cells and NK cells | Tiragolumab | Fully human IgG1 antibody | – |
| CD137 | Tumor cells, CD4+ and CD8+ T cells, Foxp3+ Tregs, NK cells, and DCs | Activate and proliferate monocytes and NK cells, promote T cell activation, proliferation, and differentiation, and also induce T cell apoptosis | Utomilumab | IgG2 monoclonal antibody | – |
CTLA-4, cytotoxic T-lymphocyte-associated protein 4; PD-1, programmed cell death protein-1; PD-L1, programmed cell death 1 ligand; TIM-3, T cell Ig and mucin-domain-3-containing molecule 3; LAG-3, lymphocyte-activation gene 3; GITR, glucocorticoid-induced TNFR-related protein; IDO1, indoleamine 2, 3-dioxygenase 1; TIGT, tyrosine-based inhibitory motif domain; Tregs, regulatory T cells; NK cells, nature killer cells; TILs, tumor infiltrating lymphocytes; MDSC, myeloid suppressor cells.