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Multiple myeloma (MM), a cancer of the bone marrow, is categorized as the second most common hematological malignancy of adults in the Western world. Despite dramatic improvements in immunotherapies in the field of cancers, MM immunotherapy has not been promising until now. Recent clinical studies of immune checkpoint inhibitor therapy, either alone or in combination with anticancer drugs, showed excessive side effects or low efficacy, particularly in advanced MM patients. In this context, lymphocyte levels of exhaustion markers play a pivotal role in the MM tumor microenvironment (TME). Hence in the present review, the mechanisms relevant to MM of five inhibitory molecules including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin, and mucin domain 3 (Tim-3), lymphocyte activation gene-3 (LAG-3), V-domain Ig Suppressor of T-cell activation and killer immunoglobulin-like receptors along with bispecific T-cell antibodies (BsAbs) will be discussed. Further, we summarized the underlying biology of these checkpoints in cancer and their rapidly emerging role in pathways in MM along with presenting recent clinical trials in context.

Nanotechnology-based drug delivery platforms have emerged as one of the promising approaches for the diagnosis and treatment of cancers. Furthermore, significant advancements have been achieved in the development of nanoparticle-antibody conjugates for applications in tumor imaging and immunoassays. Without a doubt, the diagnostic insight garnered from these nanoprobes will prove invaluable in determining rational therapeutic strategies. In the current experiment, we developed a breast cancer imaging probe utilizing graphene quantum dots, these quantum dots were conjugated with pembrolizumab (GQDs–pembrolizumab), a human monoclonal antibody (mAb) targeting the immune checkpoint programmed death receptor (PD-1) and its programmed death ligand-1 (PD-L1). Various techniques were employed for characterization, encompassing transmission electron microscopy (TEM), element mapping, atomic force microscopy (AFM), Fourier-transform infrared spectroscopy, and circular dichroism (CD) spectroscopy. The toxicity of nanoconjugate was evaluated using the MTT assay on HEK-293 and 4T1 cell lines. Subsequently, the synthesized nanoconjugate was radiolabeled with Technetium-99m (99mTc) to produce 99mTc-GQDs–pembrolizumab. Biodistribution and SPECT imaging were conducted to assess the pharmacokinetics and targeting efficacy of the 99mTc-GQDs–pembrolizumab in a BALB/c mouse model bearing with 4T1 tumors. The high Radiochemical purity (RCP > 95 %) and satisfactory in vitro stability demonstrate the significant potential of GQDs–pembrolizumab to form complexes with Technetium-99m. The findings from imaging and biodistribution studies demonstrated the high activity of 99mTc-GQDs–pembrolizumab at the tumor site (8.4 %ID/g), attributed to the presence of the PD-1 receptor. Furthermore, the increased radiotracer uptake was evident in the liver and spleen, both being lymphoid tissues. The suitable properties and behavior of 99mTc-GQDs–pembrolizumab suggest that it holds promise as a novel probe for the development of radiopharmaceutical-based immune checkpoint monoclonal antibodies. Additionally, it has the potential to facilitate immunotherapy for treating a wide range of cancers.

Checkpoint markers and immune checkpoint inhibitors have been increasingly identified and developed as potential immunotherapeutic targets in various human cancers. Despite valuable efforts to discover novel immune checkpoints and their ligands, the precise roles of their therapeutic functions, as well as the broad identification of their counterpart receptors, remain to be addressed. In this context, it has been suggested that various putative checkpoint receptors can be induced upon activation. In the tumor microenvironment, T cells, as crucial immune response against malignant diseases as well as other immune central effector cells, such as natural killer cells, are regulated via co-stimulatory or co-inhibitory signals from immune or tumor cells. Studies have shown that exposure of T cells to tumor antigens upregulates the expression of inhibitory checkpoint receptors, leading to T-cell dysfunction or exhaustion. Although targeting immune checkpoint regulators has shown relative clinical efficacy in some tumor types, most trials in the field of cancer immunotherapies have revealed unsatisfactory results due to de novo or adaptive resistance in cancer patients. To overcome these obstacles, combinational therapies with newly discovered inhibitory molecules or combined blockage of several checkpoints provide a rationale for further research. Moreover, precise identification of their receptors counterparts at crucial checkpoints is likely to promise effective therapies. In this review, we examine the prospects for the application of newly emerging checkpoints, such as T-cell immunoglobulin and mucin domain 3, lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T-cell activation (VISTA), new B7 family proteins, and B- and T-cell lymphocyte attenuator, in association with immunotherapy of malignancies. In addition, their clinical and biological significance is discussed, including their expression in various human cancers, along with their roles in T-cell-mediated immune responses.

Vaccines blocking malaria parasites in the blood-stage diminish mortality and morbidity caused by the disease. Here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. We used the sera of malaria self-resistant ICR mice to lethal Plasmodium yoelii yoelii 17XL for purification of their IgGs which were subsequently employed to isolate blood-stage parasite antigens that were inoculated to immunize BALB/c mice. The presence of specific antibodies in vaccinated mice serum was studied by immunoblot analysis at different days after vaccination and showed an intensive immune response to a wide range of antigens with molecular weight ranging between 22 and 250 kDa. The humoral response allowed delay of the infection after the inoculation to high lethal doses of P. yoelii yoelii 17XL resulting in a partial protection against malaria disease, although final survival was managed in a low proportion of challenged mice. This approach shows the potential to prevent malaria disease with a set of antigens isolated from blood-stage parasites.