Immune Checkpoint Cell Lines
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
Background of Membrane Immune Checkpoint
The immune checkpoint on the membrane is a necessary sensory element of the system of immunization and contributes to the process of the response to immunization. The checkpoints distribute on the plasma membrane of T cells, B cells, and natural killer cells. They bind to their ligands to activate the downstream pathway of self-tolerance and recognition of other cells, so that killer cells can identify others instead of an indiscriminate attack. Molecules of the immune checkpoint can be further divided into two subgroups according to their effects, named stimulatory checkpoint molecules and inhibitory checkpoint molecules.
Fig. 1 Schematic of common immune checkpoint modulates.1,2
Functions and Mechanisms of Membrane Immune Checkpoint
Immune checkpoints and their related pathways modulate and control the response of immunomodulatory while preserving self-tolerance through the specific binding of recognition molecules to its ligands, therefore, preventing the immune system from damaging the organism itself. However, almost all types of cancer cells can also protect themselves from lymphocytes and other killer cells via the stimulation of immune checkpoints.
Application and Pathology of Immune Checkpoint Cell Lines
Many cancer cells can evade the damage from the immune system by overexpressing ligands that inhibit these checkpoints and suppress the T-cell attack. Therefore, research on checkpoint molecules and their ligands or blockades can exert great benefits in the therapeutic treatment and clinical intervention of tumors.
Published Data
| Paper Title | Immune checkpoint blockade in HIV |
| Journal | eBioMedicine |
| Published | 2022 |
| Abstract | Antiretroviral therapy (ART) can significantly restore immune function and prolong life expectancy in HIV-infected individuals. However, ART cannot completely cure HIV, and the improvement of immune function depends on long-term and life-long drug use. In theory, achieving long-term stable control of HIV without ART requires the patient's own strong T cell function, but even during ART treatment, HIV infection will cause severe immune failure. This contradiction makes HIV extremely difficult to cure. In previous studies, it was found that immune checkpoint blockade in cancer patients significantly increased tumor-directed T-cell responses, thereby achieving effective and significant clinical therapeutic effects. This makes HIV symptom relief a possible target by driving the recovery of HIV-specific T cells and reversing HIV latency. Experimentalists summarize recent evidence on the role of immune checkpoints in persistent HIV symptoms and discuss the possibility of using immune checkpoint blockade (ICB) to enhance T cell responses to alleviate or even cure persistent HIV by ART. |
| Result |
In conclusion, extensive preclinical data underscore the potential of ICBs against persistent simian immunodeficiency virus (SIV) and HIV infection. Clinical data from prognosis for people with HIV (PWH) on ART with and without malignancy suggest modest effects in reversing HIV latency, most pronounced to date seen in individuals receiving combination blockade including anti-CTLA-4 effect. To what extent and by what mechanism ICBs durably enhance HIV-specific T-cell function are still being explored, but preliminary data suggest this may only occur in a subset of treated individuals. This is consistent with findings in cancer therapy, where anti-PD-1 antitumor response rates range as high as 4-70%, depending on tumor pathology. While targeting more than one inhibitory pathway may be superior to the single-drug blockade, the enhanced effect may come at the cost of increased toxicity, and it is unclear how these findings will be translated into clinical strategies for HIV cure. A large and rapidly increasing number of ongoing clinical trials investigating combination therapy in patients with malignancies will provide more information on whether combined blockade can improve clinical efficacy relative to toxicity, but given the favorable prognosis of PWH after ART, immune tolerability was much lower. Therefore, single or combined blockade of HIV immune checkpoints has focused on understanding how disrupting negative signaling or enhancing co-stimulatory signaling might help enhance HIV-specific T-cell function and/or eliminate latently infected CD4+ T-cells. With future improvements in risk reduction or new approaches to safely deliver ICBs to PWH without cancer, combinations of immune checkpoint antibodies may become viable clinical strategies to be tested in HIV cure research.
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Fig. 2 Immune checkpoint antibodies have two distinct effects in the setting of HIV on ART.3,4
References
- Xu, Feng, et al. "Immune checkpoint therapy in liver cancer." Journal of Experimental & Clinical Cancer Research 37 (2018): 1-12.
- Image retrieved from Figure 1 " Illustration of stimulatory and inhibitory immune checkpoints between T-cells, APCs, and cancer cells. " Xu, et al. 2018, used under CC BY 4.0. The original image was modified by extracting and the title was changed to " Schematic of common immune checkpoint modulates.".
- Gubser, Celine, et al. "Immune checkpoint blockade in HIV." EBioMedicine 76 (2022).
- Image retrieved from Figure 1 " Dual Role of ICB in HIV. " Gubser, et al. 2022, used under CC BY 4.0. The original image was modified by extracting and the title was changed to " Immune checkpoint antibodies have two distinct effects in the setting of HIV on ART.".
