Immune Receptor Stable Cell Lines: A Useful Tool in Aiding Anti-Tumor Novel Drugs Development

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers.

Fig. 1 Immune checkpoint receptors and their ligands. (Cai, et al., 2021)

Inhibitory Checkpoint Molecules

In the last decade, inhibitory immune checkpoints have emerged as pivotal molecules preventing tumor attack by the immune system. Cancer cells exploit immune-inhibitory molecules to contrast immune interventions and induce tumor tolerance. Additionally, inhibitory checkpoint molecules are targets for cancer immunotherapy because of their potential for use in multiple types of cancers. Molecular agents that target these checkpoints represent a new frontier for cancer treatment. Immune checkpoint-targeted therapy has been shown to be helpful for the treatment of selected and even histologically different types of cancer.

Immune Checkpoint Pathways

Recent advances in cancer immunotherapy involve blockade of CTLA4 (also known as CD279) and PD-1 in order to reverse T-cell exhaustion and reinvigorate immunity in metastatic melanoma and lung cancer. First, T-cell responses rely on TCR-dependent recognition of MHC/peptide complexes on antigen-presenting cells (APCs). Further engagement of costimulatory and co-inhibitory molecules guarantees the onset and limitation of T-cell activities, supporting the functions of immune checkpoints. Initial studies focused on relieving the immunosuppressive brake applied by the co-inhibitory CTLA-4 and PD-1 receptors. CTLA-4 is expressed by activated Tregs and exhibits competitive binding with stimulatory CD28 ligands (CD80/CD86). PD-1 is expressed by activated and exhausted T cells, and binding to its ligands PD-L1 and PDL-2 directly inhibits TCR signaling through SHP2-mediated dephosphorylation of proximal signaling elements. Notably, recent findings have identified CD28 as a convergent regulatory target for both CTLA-4 and PD-1 and have demonstrated the regulation of intratumoral T-cell trafficking by PD-1.

Fig. 2 The mechanism of immunotherapy regulation based on immune checkpoint pathways (PD-1 and PD-L1). (Wang, et al., 2021)

Immune Receptor Stable Cell Lines

To date, many new immune checkpoints have been identified and developed as potential therapeutic targets, such as PD-1/PD-L1, TIM-3, LAG-3, VISTA, and IDO1. To accelerate the progress of immune checkpoint protein research and the development of relevant cancer therapies, we have developed stable cell lines expressing the most popular human, mouse and crab monkey immune checkpoints that can help you make progress in areas including:

Research on immune related diseases and finding therapies or exploring drugs.
Screening antibodies of immune related proteins via flow cytometry, immunocytochemistry or western blotting.
Studying mechnisms of immune response.

Development of Novel Immune Checkpoint-Based Drugs

Novel immune checkpoint molecules and drugs that regulate the expression or function of these molecules may have promising clinical applications. Drugs or drug candidates that inhibit or block inhibitory checkpoint molecules are sometimes known as checkpoint inhibitors or the immune checkpoint blockade.

Inflammatory immune responses are often difficult to treat specifically because of their highly complex multitarget networks. There are two well-known immune checkpoint receptors that have been actively studied. One of the most widely studied anticancer targets is the important immune checkpoint molecule PD-1 and its ligand PD-L1. Another important checkpoint molecule is CTLA-4. Antibodies targeting these molecules are currently the most effective treatments available. Corresponding antibodies can inhibit the functions of the receptors and enhance the immunity of antitumor cells. Moreover, multiple additional immune checkpoints are being studied as promising targets for anticancer therapy.

In addition to the above main immune checkpoints, immunotherapies targeting other molecules, such as TIM-3, LAG3, KIR, GITR, VISTA, IDO, 4-1BB, and tryptophan 2,3-dioxygenase, are also being explored. For example, LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in the human immune system.

Creative Biogene has launched the most commonly used immune checkpoint stabilized cell lines to help customers accelerate the development and approval of relevant antibody drugs in immunotherapy. Please contact us for more information about Immune receptor stable cell lines products.

References:

Wang, Y.; et al. Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development. Acta Pharm Sin B. 2021 Oct;11(10):2957-2972.
Cai, X.; et al. Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases. Front Genet. 2021 Nov 30;12: 785153.

* For research use only. Not intended for any clinical use.

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Immune Receptor Stable Cell Lines: A Useful Tool in Aiding Anti-Tumor Novel Drugs Development

Inhibitory Checkpoint Molecules

Immune Checkpoint Pathways

Immune Receptor Stable Cell Lines

Development of Novel Immune Checkpoint-Based Drugs

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