Antibody–drug conjugates (ADCs) represent a groundbreaking advancement in cancer therapeutics, combining the high specificity of monoclonal antibodies with the potent cytotoxic effects of chemotherapy. This innovative approach aims to selectively target cancer cells while minimizing damage to healthy tissues, thereby overcoming the limitations of traditional chemotherapy.

ADCs are engineered molecules composed of three critical components: a monoclonal antibody that specifically binds to tumor-associated antigens, a cytotoxic payload capable of killing cancer cells, and a chemical linker that ensures the stability of the drug until it reaches the target. Upon binding to the target antigen on the surface of cancer cells, the ADC is internalized, and the cytotoxic drug is released intracellularly, leading to targeted cell death.

Clinically approved ADCs such as trastuzumab emtansine (T-DM1), targeting HER2 in breast cancer, and gemtuzumab ozogamicin, targeting CD33 in acute myeloid leukemia, have demonstrated substantial improvements in treatment outcomes, including enhanced progression-free survival and reduced systemic toxicity. These successes underscore the importance of precise antigen selection and the continuous evolution of ADC design strategies.

Despite their promise, ADC development is challenged by factors such as tumor antigen heterogeneity, multidrug resistance, and the need for stable yet cleavable linkers. However, advancements in antibody engineering, site-specific conjugation, and next-generation payloads are rapidly addressing these hurdles. Novel ADCs with bispecific targeting capabilities and innovative payload mechanisms are currently in development, further expanding their therapeutic potential.

This work emphasizes the role of HER2 and CD33-targeted ADCs as models of precision oncology, illustrating how these agents are redefining the landscape of chemotherapy. As research progresses, ADCs are expected to play an increasingly vital role in personalized cancer treatment, offering a powerful blend of specificity, efficacy, and safety.

Allergic conditions are immune hypersensitivity reactions triggered by otherwise harmless environmental substances such as pollen, dust, food, or insect venom. Central to these reactions are specific antibodies—particularly Immunoglobulin E (IgE)—which mediate Type I hypersensitivity. IgE is produced upon initial exposure to an allergen through the activation of B cells, aided by T helper 2 (Th2) cells and cytokines like IL-4 and IL-13. Once synthesized, IgE binds to high-affinity FcεRI receptors on mast cells and basophils, sensitizing them to future exposures.

Upon re-exposure, allergens cross-link the IgE molecules on these sensitized cells, leading to degranulation and the release of inflammatory mediators such as histamine, prostaglandins, leukotrienes, and cytokines. These mediators are responsible for the hallmark symptoms of allergy, including itching, wheezing, swelling, and in severe cases, anaphylaxis.

Beyond IgE, emerging research suggests roles for IgG subclasses, particularly IgG4, in immunomodulation during allergen-specific immunotherapy, and IgA in mucosal immune responses, adding complexity to our understanding of antibody function in allergic diseases.

Therapeutically, targeting IgE has revolutionized allergy management. Monoclonal antibodies like omalizumab bind free IgE, preventing its interaction with FcεRI receptors and thus reducing mast cell and basophil activation. Newer approaches are exploring anti-IL-4/IL-13 therapies, Fc receptor blockers, and allergen desensitization strategies to reduce IgE synthesis and allergic inflammation.

Understanding the antibody-mediated immune mechanisms in allergy not only improves diagnosis and risk stratification, but also facilitates the development of personalized therapies that are safer and more effective. Continued research into antibody dynamics in hypersensitivity responses holds promise for reducing the global burden of allergic diseases, which are on the rise due to urbanization, pollution, and changing lifestyles.

Hepatitis A virus (HAV) remains a global health concern, especially in regions with poor sanitation and limited access to clean water. Although self-limiting in most cases, HAV infection can result in acute liver failure, particularly in adults and immunocompromised individuals. The immune response, particularly the production of antibodies, plays a central role in both natural immunity and vaccine-induced protection against HAV.
Antibodies generated against HAV surface antigens are crucial in neutralizing the virus and preventing infection. Licensed inactivated and live-attenuated HAV vaccines have been highly successful in inducing long-lasting immunity by stimulating robust antibody responses. The role of neutralizing IgG antibodies is well established in conferring lifelong protection, and vaccine-induced memory B cells contribute to rapid response upon re-exposure.
In addition to prophylactic vaccination, antibody-based interventions can support antiviral therapies, particularly in post-exposure prophylaxis. The use of passive immunization through HAV-specific immunoglobulins provides temporary protection and is especially useful for individuals at high risk or those with contraindications to vaccination.
Animal models have significantly contributed to understanding the immunogenicity of HAV vaccines and the mechanisms of antibody-mediated viral clearance.
While antiretroviral therapy (ART) is primarily associated with HIV, HAV-HIV coinfection presents a unique challenge where ART’s immune modulation may influence HAV infection outcomes. Monitoring antibody titers and HAV vaccine responsiveness in ART-treated individuals is essential for effective immunization strategies in immunocompromised populations.
Novel approaches such as monoclonal antibody development targeting HAV capsid proteins are under exploration, offering potential in both treatment and prophylaxis. These innovative therapies could be particularly valuable during outbreaks or in regions with limited vaccine access.
In conclusion, antibodies are at the core of effective HAV prevention and therapeutic strategies. Continued research into vaccine optimization, monoclonal antibody therapy, and immune response modulation is essential to combat HAV infections across diverse populations.

Introduction: N-linked carbohydrate structures in the Fc-region of human IgG fine tune effector functions such as antibody-dependent complement activation and Fc-receptormediated phagocytosis. The Nordenfelt laboratory recently identified and characterized a human monoclonal (mAb) IgG antibody directed towards the M protein, a surface protein and virulence factor of Streptococcus pyogenes (GAS). These were isolated from memory B cells from an individual who had recovered from a GAS infection. One of the mAbs, Ab25, not only binds M protein with high affinity, but also promotes efficient phagocytosis of the bacteria in vitro. This is attributed to a natural bi-specificity towards two different M protein epitopes.

Methods: Chemoenzymatic engineering was used to remove all Fc glycans on Ab25, Ab49 (monospecific mAb against M protein), and omalizumab (IgG mAb against IgE) as the control, and then generate homogenous glycoforms (G0, G0-afuc, G2, G2S2) through click chemistry. Validation of glycosylation pre- and post engineering was performed using LC-MS. These were subsequently tested using flow cytometry-based bacterial binding, phagocytosis using THP-1 cells, and complement factor C1q deposition assays.

Results: Original mAb glycosylation and generated glycoforms were validated using LC-MC. Binding experiments revealed that only deglycosylation had any major effects of binding to bacteria; the phagocytosis experiment revealed that the internalization, but not association, of bacteria to THP-1 was influenced by antibody glycoform; and C1q deposition was gradually decreasing in correlation with the size and complexity of the glycans.

Conclusions: Human IgG mMAbs against GAS, as well as omalizumab, could be converted to homogenous glycoforms. mAb glycoform clearly influences internalization into phagocytes as well as complement binding. This has important implications for the development of anti-infective mAbs, and highlights mAb glycan engineering as a modality when developing IgG-based therapeutic antibodies.

Introduction: Monoclonal antibodies (mAbs) have become pivotal in cancer therapy due to their ability to recognize tumor-associated antigens, triggering immune responses or disrupting signaling pathways essential for tumor growth and survival. Over recent decades, mAbs have been engineered as carriers for cytotoxic agents, enabling targeted delivery, reducing off-target toxicity, and expanding the therapeutic window of chemotherapeutics. Since antitumor efficacy often correlates with drug payload, this study explores a strategy to enhance drug delivery by conjugating a mAb to a drug-loaded nanostructured lipid carrier (NLC) via a maleimide-based reaction.
Methods: NLCs were produced consisting of a disordered solid lipid matrix (comprising blended solid and liquid lipids) and a surfactant-containing aqueous phase, designed to encapsulate poorly soluble drugs. After loading the maleimide lipid containing NLCs with the topoisomerase I inhibitor SN-38, nanoparticles were incubated with Denintuzumab, a CD19 specific antibody, in the presence of a reducing agent. The mixture was next purified through size exclusion chromatography.
Results: The resulting antibody-NLC conjugates are monodisperse (with a PDI of 0.27), exhibit a hydrodynamic diameter of ~140 nm, and retain high target specificity.
Conclusions: It is feasible to conjugate monoclonal antibodies to drug-loaded NLCs. Ongoing work focuses on loading these nanoparticles with the topoisomerase I inhibitor SN-38 and evaluating the targeted delivery efficacy of these nanoparticles in tumor models.

Zika virus (ZIKV), a mosquito-borne flavivirus, has emerged as a significant global health concern due to its association with severe neurological complications, including congenital microcephaly and Guillain–Barré syndrome. Despite recurring outbreaks across multiple continents, there are currently no licensed vaccines or specific antiviral therapies available. Previous intrinsic disorder profiling of the ZIKV proteome has revealed that several viral proteins harbour substantial intrinsically disordered regions (IDRs), with particularly high disorder propensity in the non-structural proteins NS4B and NS5, and in the C-terminal tail of the capsid protein. These flexible regions facilitate dynamic interactions with host factors, playing a pivotal role in viral replication, immune modulation, and evasion mechanisms. In this study, we present an open-access, end-to-end in silico antibody design pipeline specifically tailored to target these disordered viral proteins. Consensus IDR prediction was performed using IUPred3, flDPnn, PONDR, and IDPpred, enabling the identification of epitope-rich disordered segments. Structural ensembles for these regions were generated using AlphaFold2 modelling followed by FlexServ sampling to capture conformational heterogeneity. B-cell epitope profiling (BepiPred-3.0, ElliPro) was employed to identify accessible and potentially immunogenic regions, which were then docked to human germline antibody scaffolds sourced from SAbDab using HADDOCK 2.4 and ClusPro. Paratope optimisation was achieved with ABpredict2, while developability and manufacturability assessments were performed using Thera-P. Preliminary docking and scoring indicate that several candidate antibodies display predicted nanomolar-range affinities for the NS4B N-terminal disordered segment and the capsid tail epitopes, with favourable stability and developability profiles. This work demonstrates the feasibility of computational antibody engineering against naturally flexible ZIKV proteins, highlighting the potential of targeting the viral “dark proteome” to develop novel therapeutic interventions.

SARS-CoV-2 remains in circulation 5 years after the first cases of COVID-19 were reported, during which time several variants have been selected with mutations accumulating especially in the more accessible S1 subunit of the Spike protein (S). Consequently, current vaccine platforms have been updated to ensure effectiveness against the Omicron XBB.1.5 variant, highlighting the need for ongoing surveillance and updates of the antigens included in the immunization strategies. To overcome this limitation, we analyzed in a SARS-CoV-2-infected human cohort the immunogenicity of the highly conserved membrane-proximal external region (MPER) of the S2 subunit of the Spike, which is conserved across the Orthocoronavirinae subfamily. A portion of the patients, even if weakly, did elicit antibodies against the MPER. Additionally, we characterized its structure in a low-polarity environment and in lipid membranes, as well as showing its fusogenic potential, confirming its active involvement in the viral infection process. Therefore, we report the suitability of the MPER as a target for vaccination. Considering the impact that lipid membranes may have on the structure of this region, we assessed its expression in the membranes of eukaryotic cells. For that, we designed wild-type and modified S2-derived DNA sequences including the MPER. The results obtained support the feasibility of designing vaccines focused on the conserved MPER region.

Introduction:
Monoclonal antibody (mAb) therapies, including immune checkpoint inhibitors and anti-epidermal growth factor receptor (EGFR) agents, are increasingly used in oral squamous cell carcinoma (OSCC) [1]. Response rates vary, highlighting the need for predictive biomarkers to guide patient selection [2,3]. This review summarises current evidence linking biomarker profiles with mAb outcomes in OSCC.

Methods:

A PRISMA-guided search of PubMed, ScienceDirect, and Web of Science identified English-language studies published within the past five years on adult OSCC treated with mAbs, reporting biomarker associations with clinical outcomes. Of the 502 records screened, 5met inclusion criteria.

Results:

Analysis of recent evidence highlights several biomarkers with predictive value for mAb and immunotherapy response in OSCC. In recurrent disease treated with nivolumab (n = 64), Tachinami et al. found that a post-treatment neutrophil-to-lymphocyte ratio (NLR) ≥ 5 was associated with poorer survival [4]. Dou et al. reported that EGFR mutations and chromosome 11q13 amplification correlated with reduced progression-free survival (PFS) and a lack of clinical benefit in patients receiving anti-PD-1 therapy [5]. In locally advanced OSCC, Xiang et al. achieved a major pathological response (MPR) rate of 69.0% and pathological complete response (pCR) rate of 41.4% with camrelizumab plus chemotherapy, with higher rates in programmed death-ligand 1 (PD-L1)-positive patients [6]. Huang et al. reported MPR 60% and pCR 30% with toripalimab plus chemotherapy, with a PD-L1 combined positive score (CPS) > 10 and increased tertiary lymphoid structures predicting response [7]. Ju et al. observed MPR 40% with camrelizumab and the vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor apatinib, with all PD-L1 CPS > 10 patients responding [8].

Conclusion:
PD-L1 expression, tertiary lymphoid structures, NLR, and genomic alterations may guide mAb therapy selection in OSCC. Evidence is limited by few studies and heterogeneity; larger prospective trials are needed to confirm clinical utility.

Chandipura virus (CHPV), a neurotropic member of the Rhabdoviridae family, has emerged as a significant public health concern in the Indian subcontinent due to its rapid progression to encephalitis and high fatality rates. Recent analysis of its dark proteome revealed a substantial presence of intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs), particularly within the phosphoprotein (P), which exhibited the highest intrinsic disorder propensity among all CHPV proteins. IDPs are characterized by conformational flexibility, enabling them to mediate multiple and transient interactions with host factors, often via molecular recognition features (MoRFs). Such properties make them crucial for viral replication, immune evasion, and host machinery manipulation. In this study, we extend our findings toward an in silico pipeline for IDP-based antibody design targeting the CHPV P protein. Consensus IDR prediction, coupled with MoRF mapping, was integrated with epitope mapping algorithms to identify disordered yet immunogenic regions. Structural ensembles generated using AlphaFold2 and disorder-refined molecular dynamics simulations using Gromacs force field enabled the modeling of conformational variability for antibody docking. This approach facilitates the rational selection of epitope-rich, conformationally adaptable targets for monoclonal antibody engineering. Our findings highlight that targeting IDP regions traditionally overlooked in structure-based vaccine design, offers a novel paradigm for CHPV immunotherapeutics, potentially overcoming antigenic variability and functional plasticity.

Background: The convergence of immuno-oncology and tumor imaging represents a paradigmatic shift in cancer management, where therapeutic antibodies serve dual roles as both treatment modalities and diagnostic tools. This field has witnessed unprecedented growth, with bispecific antibodies, antibody-drug conjugates (ADCs), and radioimmunotherapy emerging as transformative approaches.

Methods: Recent advances encompass multiple innovative platforms addressing tumor heterogeneity and resistance mechanisms. Bispecific antibodies demonstrate remarkable versatility by simultaneously engaging immune effector cells and tumor-associated antigens, achieving tumor-specific cytotoxicity without MHC restriction. Next-generation ADCs incorporate dual-payload designs and novel linker technologies, enabling synergistic cytotoxic effects while minimizing off-target toxicity. Radioimmunotherapy has evolved with theranostic strategies utilizing single antibodies conjugated to different radioisotopes for combined imaging and therapy.

Imaging Innovations: Molecular imaging modalities have revolutionized cancer detection through antibody-based approaches. Fluorescence-guided surgery utilizes tumor-specific antibodies conjugated to near-infrared fluorophores, enabling real-time intraoperative tumor visualization. Immuno-PET/SPECT combines nanomolar sensitivity with antibody specificity, enabling the assessment of whole-body biomarker distribution and the prediction of treatment response. These platforms support precision medicine by enabling patient stratification and dynamic monitoring of antigen expression heterogeneity.

Clinical Impact: The integration of therapeutic and diagnostic antibodies has demonstrated clinical success, with over 200 marketed antibody therapeutics currently available. Checkpoint inhibitors targeting PD-1/PD-L1 pathways have established immunotherapy as a cornerstone of cancer treatment, while emerging targets, including LAG-3 and CD47, offer expanded therapeutic opportunities.

Conclusions: The synergistic integration of immuno-oncology and tumor imaging through antibody-based platforms represents a transformative approach to cancer care, enabling personalized treatment strategies based on real-time tumor characterization and overcoming current therapeutic limitations.