Cancer is a severe public health issue and one of the main causes of morbidity and mortality worldwide. However, the effect of chemoradiotherapy for cancer or tumor may be limited due to serious side effects and drug resistance. Therefore, it is essential to develop novel therapies for cancer treatment.
In 2018, James P. Allison and Tasuku Honjo’s research on the immune checkpoints programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) demonstrated that they acted as a “brake” in immune function and suggested that immune checkpoint inhibition may reactivate T cells and eliminate cancer cells more effectively. Preclinical studies showing decreased tumor growth and improved survival with CTLA-4 or PD-1 pathway blockade provide the rationale for immune checkpoint inhibition for cancer treatment.
Truly, the discovery of the checkpoint molecules CTLA-4 and PD-1 has pushed the pharmaceutical industry to develop specific inhibitors for cancer treatments, driving many scientists and physicians to further explore this area in recent years. Especially notable is the significant accomplishment in the treatment of malignant melanoma, where no advance has been made in the therapy of this terrible illness in more than 30 years. Besides, monoclonal antibodies that block CTLA-4 or PD-1 are in development for other tumor types, including kidney cancer, prostate cancer, and head and neck cancer. Other agents specifically targeting PD-L1 are also in development.
While CTLA-4 and PD-1 blockade has proved successful in improving survival rates, many patients do not respond or develop resistance to these interventions. Pre-clinical and clinical studies, on the other hand, have shown that combining two distinct immunological checkpoints as therapeutic targets, such as CTLA-4 and PD-1, LAG-3 and PD-1, TIM-3 and PD-1, and A2AR/PD-L1, has great potential.
However, the path is still rocky. Many issues and questions arose during the experience with immunotherapeutic drugs targeting immunological checkpoint molecules. For instance, it is still not clear how to monitor the success of therapy, and many patients do not respond or develop resistance to interventions of PD-1 and CTLA-4. There is no doubt that these questions require further research. Therefore, studies focused on immune checkpoint molecules are under intensive investigation. Creative Biolabs is committed to providing immunotherapeutic development services, such as immune checkpoint-based antibodies, molecules, biomarkers, peptides, and proteins, to support research on cancer immunotherapy.
In conclusion, immune checkpoint inhibition is a promising approach for treating cancer, with a considerable proportion of patients benefiting, despite its limitations in clinical use. Further studies on immune checkpoints are needed to address the existing problems and help more patients with tumors and other diseases.