[Advances of monoclonal antibodies and analysis of marketed antibody drugs].

In recent years, there has been a frequent occurrence of various epidemics worldwide such as COVID-19, monkeypox, influenza, and others additionally, there has been an increase in the number of new patients diagnosed with various types of tumors. Traditional drugs have limited effectiveness against emerging infectious diseases, tumors, and autoimmune diseases. However, with the emergence of hybridoma technology, monoclonal antibodies have achieved extensive applications and antibody drugs are playing an important role in modern medicine. Monoclonal antibodies have undergone various development stages, starting from mouse-derived antibodies to human-mouse chimeric antibodies, humanized antibodies, and ultimately human antibodies. Throughout this process, their immunogenicity has gradually decreased, while their safety for human use steadily increased. Fully human antibodies are currently the safest form of antibody, because their sequences all come from human sources and they do not induce human anti-murine antibody reactions. With the advance of genetic engineering technology, flow cytometry coupled to single B cell gene amplification technology has made it easier to construct and screen for fully human monoclonal antibodies. The development of antibody drugs has provided new opportunities, and the market for monoclonal antibody drugs will further expand. This article reviews the research progress of monoclonal antibodies and presents information on the 163 monoclonal antibody drugs approved by the United States Food and Drug Administration (FDA) as of Oct 1st, 2023. The aim is to offer new insights for the development and production of monoclonal antibodies in China.

Supramolecular assembly of dendronized spiropyrans in aqueous solutions into nanospheres with photo- and thermo-responsive chiralities.

Tailoring the amphiphilicity of a molecule through external stimuli can alter the balance between self-association and repulsion, resulting in different propensities for its assembly. Here we report on the supramolecular assembly of a series of dendronized spiropyrans (DSPs) in water. These DSPs carry 3-fold dendritic oligoethylene glycols (OEGs) with either methoxyl or ethoxyl terminals for different hydrophilicities, and contain an Ala-Gly dipeptide to provide the chirality. These dendronized amphiphiles form supramolecular nanospheres in aqueous solutions with remarkable induced chirality to a level of 1.0 × 106 deg cm2 dmol-1. They can be tuned reversibly through photoisomerization of the spiropyran moieties from the hydrophobic SP form into the hydrophilic MC form, and can even become chirally silent through thermally mediated collapse of the dendritic OEGs. Photoisomerization of the spiropyran moieties in these DSPs is accompanied by simultaneous changes of UV absorption, fluorescence emission, supramolecular chirality and aqueous solution colors. These supramolecular nanospheres exhibit characteristic thermoresponsive behavior due to thermal collapse of the dendritic OEGs with their cloud point temperatures (Tcps) being dependent on the overall hydrophilicity of the molecules and also the aggregate morphologies resulting from how dendritic OEGs are wrapped around the aggregates. Both photo-irradiation-mediated isomerization of the spiropyran moieties and thermally mediated dehydration and collapse of the dendritic OEGs influence the amphiphilicity of these DSPs and their solvation by water, leading to varied driving forces for their assembly. NMR, circular dichroism (CD) and fluorescence spectroscopy techniques, as well as DLS and AFM techniques are combined to follow the supramolecular assembly and illustrate the aggregation mechanism. All experimental results demonstrate that the reversible chirality of the aggregates originates from the balance between dendritic OEGs and spiropyran moieties against water solvation.

Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge.

Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.

Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers.

Smallpox, an epidemic disease caused by Orthopoxvirus variola, was eradicated worldwide through immunization. The immunization against smallpox was discontinued in 1980. However, incidences of monkeypox virus infection in humans have occurred sporadically, and there is also great fear that engineered forms of poxvirus could be used as biological weapons. Therefore, monoclonal antibodies against poxvirus are urgently needed for the detection and treatment of poxvirus infection. The vaccinia virus' extracellular envelope protein A33 is a potential candidate for a subunit vaccine. We used multi-fluorescence-labeled tetrameric A33 antigen to identify rare poxvirus-specific memory B cells from the PBMC of volunteers with vaccinia virus immunization more than 40 years ago. Despite extremely low frequencies of the poxvirus-specific memory B cells, we successfully sorted A33 tetramer-labeled single memory B cells and reconstructed the antibodies with the single-cell RT-PCR of the B-cell receptor. Among the monoclonal antibodies, one clone H2 exhibited high specificity and affinity with A33. H2 efficiently inhibited viral infection and spread in cells. Passive immunotherapy of H2 in mice protected mice from lethal infection when administered either prophylactically or therapeutically. These results suggest the potential of anti-A33 human-antibody-based detection and therapeutics for poxvirus infection.