Our promise to you:
Guaranteed product quality, expert customer support.
24x7 CUSTOMER SERVICE
CONTACT US TO ORDER
During the development and progression of cancer, tumors continue to evolve and may exhibit multiple mechanisms to evade tumor immune surveillance and suppress anti-tumor immune responses. A major mechanism of tumor immune evasion involves the engagement of immune checkpoint pathways. Under physiological conditions, immune checkpoint molecules regulate the immune system, suppressing the immune response after successful mitigation of an infection or other threat. Immune checkpoint proteins play important roles in inflammatory responses and cancer immunotherapy. Many immune checkpoint proteins are dysregulated in cancer and infectious diseases, including CTLA-4, PD-1/PD-L1, lymphocyte activation 3 (LAG-3), TIM-3, VISTA, and Indoleamine-2,3 dioxygenase 1 (IDO1). Currently, several antibodies and small compounds targeting various immune checkpoint proteins are in clinical development.
At Creative Biogene, we set out to help immuno-oncologists test their novel checkpoint inhibitor drug candidates by providing them with the tools to create robust reporting assay systems. Drawing on decades of experience in cell line engineering and drug discovery, we develop immune checkpoint stable cell lines that endogenously express high levels of immune checkpoint molecules.
The development of cancer immunotherapy has emerged as an exciting new approach to treating cancer. Inhibiting immune checkpoints is one of the most promising approaches to unlocking the potential of anti-tumor immune responses. Immune checkpoint blockade is a monoclonal antibody that binds to checkpoint molecules on the surface of immune cells and tumor cells. In contrast to traditional treatment strategies, immune checkpoint inhibitors (ICIs) fight tumor cells by reviving the host immune system. Several antibodies and small compounds targeting various immune checkpoint proteins are in clinical development, including B7H3, CD39, CD73, adenosine A2A receptor, and CD47. Stable cell lines that express immune checkpoint molecules have become invaluable tools in understanding these mechanisms and developing novel therapies.
Figure 1. Immune checkpoint inhibitors approved by FDA. (Shiravand Y, et al., 2022)
Applications for immune checkpoint stable cell lines include:
Case Study 1
Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1) are immune checkpoint proteins expressed in T cells. Studies have found that CTLA4 intrinsic to tumor cells can regulate the expression of PD-L1 and cell proliferation, and anti-CTLA4 antibodies may lead to the activation of the EGFR pathway in cancer cells by binding to CTLA4 intrinsic to tumor cells.
Researchers used the MTT assay in A549 cells, A549 CTLA4 KO cells, and A549 CTLA4 overexpressing (OE) cells. Anti-CTLA4 antibody treatment was found to promote cell proliferation in A549 cells, more so in A549 CTLA4 overexpressing cells, but not in A549 CTLA4 KO cells (Figure 2A). Anti-CTLA4 antibodies increased xenograft tumor growth compared with control IgG treatment. Anti-PD-1 antibodies reduced xenograft tumor growth (Figure 2B). The combination of anti-CTLA4 and anti-PD-1 antibodies increased PD-L1 expression in tumor tissue (Figure 2C).
Figure 2. Effects of anti-CTLA4 antibodies on cell proliferation and tumor growth in the absence of adaptive immunity. (Zhang H, et al., 2019)
Case Study 2
AGEN1884 is a novel IgG1 antibody directed against CTLA-4. It potently enhances antigen-specific T cell reactivity, which can be enhanced when combined with other immunomodulatory antibodies. The research here shows that AGEN1884 can effectively modulate the immune synapse by antagonizing CTLA-4, and that combination with other immunomodulatory antibodies can further enhance the effects of the immune synapse.
Figure 3. Fcγ receptor signaling in CTLA-4-expressing cells using AGEN1884. The Jurkat cell line, genetically engineered to express FcγR upstream of the NFAT-dependent luciferase reporter, was cocultured with CTLA-4-expressing cells and increasing doses of AGEN1884 or isotype control. Signaling through (A) FcγRIIIA-V158-, (B) FcγRIIIA-F158-, or (C) FcγRIIA-H131-expressing cells was assessed based on luciferase expression. (Gombos R B, et al., 2018)
Q: What are immune checkpoints?
A: Immune checkpoints are molecules present on immune cells that help regulate the immune response. These molecules act as "brakes" or "checkpoints" to prevent the immune system from attacking normal cells in the body excessively. They play a crucial role in maintaining self-tolerance and preventing autoimmunity.
Q: What are immune checkpoint inhibitors used for?
A: Immune checkpoint inhibitors are a type of immunotherapy that block inhibitory signals and enhance the anti-tumor immune response. They help to overcome the evasion tactics of cancer cells by boosting the immune system.
Q: Which immune checkpoint inhibitors have been approved for cancer treatment?
A: Drugs targeting PD-1, PD-L1, and CTLA-4 have been approved for the treatment of various cancers. They have shown promising results in improving patient outcomes.
Q: What are immune checkpoint stable cell lines?
A: Immune checkpoint stable cell lines have proven to be invaluable tools for the development and characterization of immune checkpoint inhibitors. These cell lines are engineered to express immune checkpoint molecules, such as PD-1 or CTLA-4, enabling researchers to assess the efficacy of potential therapeutic agents that target these checkpoints in a controlled environment.
Q: What are the advantages of using these immune checkpoint stable cell lines for in vitro assays?
A: Our cell lines have excellent assay sensitivity and reproducibility and the high endogenous expression of immune checkpoint molecules in these cell lines provides physiological relevance for checkpoint assays.
| Cat.No. | Product Name | Price |
|---|---|---|
| CSC-RO0001 | Human TNFRSF9 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0002 | Human CD276 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0003 | Human VTCN1 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0004 | Human BTLA Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0005 | Human CD200R1 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0006 | Human CD80 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0007 | Human CD86 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0008 | Human TNFRSF18 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0009 | Human LAG3 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0010 | Human SPATA2 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0011 | Human CD274 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0012 | Human CD274 Stable Cell Line-HEK293T | Inquiry |
| CSC-RO0013 | Human HAVCR2 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0014 | Human C10orf54 Stable Cell Line-CHO-K1 | Inquiry |
| CSC-RO0040 | Human TIGIT Stable Cell Line-CHO-K1 | Inquiry |
Copyright © Creative Biogene. All rights reserved.