Immune checkpoint inhibitors have drawn a consider attention as an effective cancer immunotherapy, and several monoclonal antibodies targeting the immune checkpoint receptors, such as human programmed cell death-1 (hPD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), are clinically used for treatment of various cancers.
Since CTLA-4 is a critical immune check-point for restricting the cancer immune response, this inhibitory HLH peptide represents a new class of drug candidates for immunotherapy.
Recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and therapeutically separable activities of anti-CTLA-4 antibodies.
Cancer immunotherapy, particularly a class of antibodies targeting the CTLA4 and PD-1/PD-L1 negative regulators of immune response (collectively called the immune checkpoint), is one of the most promising approaches for cancer treatment and the use of immune checkpoint inhibitors (ICI) has demonstrated remarkable success in several types of cancer.
Therapies that target cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have provided unprecedented clinical benefits in various types of cancer.
Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy.
Since most malignant pleural mesotheliomas do not respond to anti-programmed cell death(-ligand)1 (PD-(L)1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy and given the recent finding of The Cancer Genome Atlas Study that pleural mesothelioma displays the highest expression of VISTA among all cancers studied, we examined VISTA expression in a large pleural mesothelioma cohort.
The immune checkpoint inhibitors (ICPIs) agents anti-T lymphocytes-associated antigen 4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) and its ligands (PD-L1/PD-L2) have opened a new scenario in the treatment of cancer.
The success of immune checkpoint inhibitors (CTLA-4 and PD-1/PD-L1) in melanoma quickly sprung to other cancer types and are considered the emerging face of oncology.
The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile.
Although checkpoint inhibitors that block CTLA-4 and PD-1 have improved cancer immunotherapies, targeting additional checkpoint receptors may be required to broaden patient response to immunotherapy.
We examine the efforts to combine current ICIs (PD-1 and CTLA-4) with novel checkpoints (TIM-3, LAG-3, VISTA, TIGIT and others), immunotherapies (CAR-T cells and Cancer Vaccines) and delivery strategies (bispecific antibodies and other delivery platforms).
When combined with anti-CTLA-4 antibody, the biomimetic and biodegradable nanoparticle enables the notable eradication of primary and deeply metastatic tumors with low systematic toxicity, thus potentially advancing the development of combined hyperthermia, PDT, and checkpoint blockade immunotherapy to combat cancer metastasis.
New loci included common variants in BRCA2 (distinct to known rare high penetrance cancer risk variants), and in CTLA4, a target of immunotherapy in melanoma.
These results documented that patients with type II and III cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies.
One of the most promising new areas of cancer treatment has been the development of immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death protein 1/programmed death-ligand 1 (PD-L1) pathways.
The success of T cell-directed checkpoint inhibitors of CTLA-4 and PD-1/PD-L1 has opened a new approach for cancer immunotherapy and resulted in extensive research on immune checkpoints.
The incorporation into clinical practice of immune-checkpoint inhibitors (ICIs), such as those targeting the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) and its ligand (PD-L1), has represented a major breakthrough in non-small cell lung cancer (NSCLC) treatment, especially in cases where the cancer has no druggable genetic alterations.
In an effort to develop a new therapy for cancer and to improve antiprogrammed death inhibitor-1 (anti-PD-1) and anticytotoxic T lymphocyte-associated protein (anti-CTLA-4) responses, we have created a telomerase reverse transcriptase promoter-regulated oncolytic adenovirus rAd.sT containing a soluble transforming growth factor receptor II fused with human IgG Fc fragment (sTGFβRIIFc) gene.
It is well established that extracellular proteins that negatively regulate T cell function, such as Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) and Programmed Cell Death protein 1 (PD-1), can be effectively targeted to enhance cancer immunotherapies and Chimeric Antigen Receptor T cells (CAR-T cells).
We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD-L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA-4) and nivolumab (targeting PD1).
We found variable numbers of CTLA-4<sup>+</sup> lymphocytes in multiple types of cancer and secondary lymphoid organs (SLOs) and other normal human tissues.
Substantial therapeutic benefits were reported among patients who participated in cancer immunotherapy clinical trials which utilized monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1).