Monoclonal Antibodies in Immunodiagnosis and Immunotherapy最新文献

One of the most potent therapeutic and diagnostic agents in contemporary medicine is the monoclonal antibody (mAb). mAbs can perform a variety of tasks in breast cancer (BC), including identifying and delivering therapeutic medications to targets, preventing cell development, and suppressing immune system inhibitors including directly attacking cancer cells. mAbs are one of the most effective therapeutic options, particularly for HER2, but they have not been well studied for their use in treating other forms of BC, particularly triple negative breast tumors. Bispecific and trispecific mAbs have created new opportunities for more targeted specific efficacy, which has a positive impact on the viability of antigen specificity. They are more versatile and effective than other forms of treatment, emerging as most popular option for treating BC. However, mAbs have a limit in treatment due to certain adverse effects, including fever, shaking, exhaustion, headache, nausea, and vomiting, as well as rashes, bleeding, and difficulty breathing. To examine the current and prospective future capacities of mAbs with regard to the detection and treatment of BC, the present review highlights advantages and disadvantages of mAb approach.

CD300a and CD300A, among the CD300 immunoglobulin (Ig)-like receptor family members in mice and humans, respectively, are expressed on myeloid cell lineage. The interaction of CD300a and CD300A with their ligands phosphatidylserine and phosphatidylethanolamine, respectively, exposed on the plasma membrane of dead cells mediate an inhibitory signal in myeloid cells. We previously reported that a neutralizing antimouse CD300a monoclonal antibody (mAb) enhanced efferocytosis by macrophages and ameliorated acute ischemic stroke (AIS) in mice. Unlike mouse CD300a, human CD300A has a single nucleotide polymorphism (SNP, rs2272111) encoding a nonsense mutation of glutamine (CD300A^Q111) instead of arginine (CD300A^R111) at residue 111. In this study, we show that the SNP frequency is 32%-35% for the heterozygous allele and 4%-5% for the homozygous alleles, except Africa. In addition, we developed a humanized antihuman CD300A mAb, named TNAX103, that recognizes both CD300A^R111 and CD300A^Q111. We show that TNAX103 interfered with the binding of CD300A^R111 and CD300A^Q111 to dead cells. In addition, the injection of TNAX103 decreased neurological scores and prolonged survival in humanized mice after middle cerebral artery occlusion. These results suggest that TNAX103 may be potentially useful for the treatment of patients expressing either CD300A^R111 or CD300A^Q111 with AIS.

Nucleophosmin (NPM1) is abundant in the nucleolus, and it shuttles between the nucleolus, nucleus, and cytoplasm to facilitate its roles in ribosome biogenesis, chromatin remodeling, DNA repair, and cell cycle regulation. It is overexpressed in various types of cancer and is related to malignancy. Furthermore, its localization is important for its cellular function and the malignant transformation of cancer cells. In this study, we describe our novel rat monoclonal antibody (mAb) 4H7, which recognizes NPM1. Our results indicated that this mAb recognizes endogenous human NPM1 in several cancer cell lines and is suitable for immunoprecipitation, immunofluorescence staining, and immunoblotting. Therefore, mAb 4H7 is expected to be useful for the functional analysis of human NPM1 in cancer and for the diagnosis of malignant transformation via expression and localization assays.

The human norovirus (HuNov) major capsid VP1comprises an S (shell) and a P (protruding) domain; the latter is responsible for virus attachment and infection. The dimeric formation of P (containing P1 and P2 subdomains) is indispensable for forming a receptor-binding pocket, enabling HuNov to dock to attachment factor histo-blood group antigens (HBGAs) on the host cell. Thus, the P-specific antibody may hamper the engagement of P and HBGA, thereby inhibiting virus infection. In this study, we developed and characterized two HuNov P-specific murine monoclonal antibodies (MAbs), namely, 5C6 and 1H12. They can bind to P protein with high affinity, as evidenced by the results of indirect fluorescent assay, western blot, and Biolayer interferometry assay. Particularly, the MAb 1H12 recognizes the P2 subdomain, whereas the 5C6 targets the distal P1. These MAbs may contribute to the exploration of novel epitopes on HuNov VP1 and to the development of new antivirals.

Congenital hypothyroidism (CH) is a major health issue that can lead to intellectual disability if not detected and treated earlier. The preliminary screening program for neonatal CH in Indonesia gave a provisional incidence of 1:2513. Newborn screening using a dried blood spot sample is the standard method for CH detection, but it has limitations. Despite the proven benefits of CH screening, Indonesia still faces significant challenges in implementing a nationwide program. This study aimed to develop a more sensitive and accessible screening method by creating monoclonal antibodies (mAbs) against the thyroid-stimulating hormone (TSH).TSH protein was isolated from newborn cord blood and confirmed by Western blot analysis. Mice were immunized with purified TSH, and hybridoma cell lines were generated through cell fusion. Hybridoma supernatants were screened for TSH-specific antibodies using ELISA. The mAb with the highest titer was purified by dialysis. Western blot analysis confirmed the presence of TSH in the isolated protein fraction at 28 kDa. Immunized mice showed a significant increase in antibody titer compared with the control group. Hybridoma clones secreting high-titer antibodies against TSH were identified. This research successfully isolated TSH and produced mAbs against it. They enable the development of rapid, point-of-care diagnostic tests, such as lateral flow immunoassays, which can provide results within minutes. It will lay the groundwork for the development of innovative CH screening tools that can significantly improve the early diagnosis and treatment of this condition, particularly in resource-limited settings.