[The humanization of medical education: publications review].

The humanization of medical education is targeted at integration of humanitarian values and approaches into system of education of medical personnel to improve their professional and personal training. This process includes education in medical ethics, development of communication skills, stress management and implementation of humanitarian disciplines into the curriculum. The humanization contributes into formation of empathy, responsibility and professionalism in future physicians that helps to better understand and consider psychological, social and emotional needs of patients. The problems of including humanitarian sciences into medical education are associated with lack of systematic approach, adequate curricula and qualified lecturers. To optimize process, it is necessary to focus on education of ideals and beliefs, development of integrated curricula and enhancement of humanitarian component of education.

Is gender primacy universal?

Emerging evidence suggests that gender is a defining feature of personhood. Studies show that gender is the primary social category individuals use to perceive humanness and the social category most strongly related to seeing someone-or something-as human. However, the universality of gender's primacy in social perception and its precedence over other social categories like race and age have been debated. We examined the primacy of gender perception in the Mayangna community of Nicaragua, a population with minimal exposure to Western influences, to test whether the primacy of gender categorization in humanization is more likely to be a culturally specific construct or a cross-cultural and potentially universal phenomenon. Consistent with findings from North American populations [A. E. Martin, M. F. Mason, J. Pers. Soc. Psychol. 123, 292-315 (2022)], the Mayangna ascribed gender to nonhuman objects more strongly than any other social category-including age, race, sexual orientation, disability, and religion-and gender was the only social category that uniquely predicted perceived humanness (i.e., the extent to which a nonhuman entity was seen as "human"). This pattern persisted even in the most isolated subgroup of the sample, who had no exposure to Western culture or media. The present results thus suggest that gender's primacy in social cognition is a widely generalizable, and potentially universal, phenomenon.

A critical perspective on institutional violence against hospitalized children: Testimonies by health professionals and family members.

The purpose of this study is to understand institutional violence (IV) in the relationships between health professionals, hospitalized children, and family members. This is a qualitative study developed at the pediatric inpatient unit of a university hospital in the city of Salvador, Bahia, Brazil. The research participants consisted of 39 health professionals who specialized in pediatrics and 10 family members of hospitalized children. Semi-structured interviews were the method used for data collection. Using discourse analysis as a basis and taking a Foucauldian perspective, the researchers observed that the expressions of IV could be traced to abusive power relations within the system. We found four discursive forms within the data set: communication problems as IV, violence through inattention and neglect, violence as an action and consequent materialization on the body, and psychological violence as a submission mechanism. Based on these findings, we argue that professionals, managers, the scientific community, and users might be able to better guarantee the safety of children by recognizing IV and effectively intervening in it.

Exploring patients and caregivers needs and experiences in oncological physiotherapy: a call for collaborative care.

PURPOSE: This study explores whether the full potential of physiotherapy is reaching cancer patients and their caregivers at all stages of the oncological process, aiming to identify gaps and opportunities for improving care. METHODS: The World Cafe co-design methodology facilitated discussions among cancer patients and caregivers. This dynamic, inclusive, and engaging approach fostered diverse perspectives and deeper insights through collaborative and flexible discussions. Sessions were recorded, transcribed, and qualitatively analyzed. RESULTS: Sixteen participants were involved (eight cancer survivors and eight caregivers). The mean age of cancer survivors was 63.8 years, while the average age of caregivers was 59.3 years. Breast cancer was the most prevalent diagnosis among patients, and most caregivers had lost their family members to cancer. Analysis revealed two primary themes: "feeling cared for" and "the role of physiotherapy in the oncological process." Key findings highlight the need for more humanized healthcare, with professionals providing support through effective communication and empathy. Significant gaps were detected in both systematic referrals to physiotherapists and their integration into care teams. Testimonies highlighted the lack of knowledge about the full potential of physiotherapy in oncology, hindering access. There was also a demand for recognizing specialized oncological physiotherapists. CONCLUSIONS: These findings highlight significant gaps in physiotherapy care for cancer survivors and caregivers, including unmet needs due to the lack of information, resources, and effective communication. Future efforts should focus on increasing the visibility of physiotherapy, integrating specialized physiotherapists into oncology teams, and enhancing the emotional education of healthcare professionals to provide more humanized care.

Development of a synthetic library of humanized nanobodies for targeted IL-6 inhibition.

Interleukin-6 (IL-6) is a cytokine that can bind to IL-6 receptor and induce pleiotropic effects. It serves as a critical biomarker, involved in inflammation amplification, tumor progression, and many other disease developments. Nanobodies, featuring small structure and high affinity, are a powerful and versatile tool in medical diagnostics and therapeutics. Here, based on a scaffold optimized for humanization and stability, we developed a synthetic phage display library that rapidly generated high-affinity and humanized nanobodies, negating the need for animal immunization. Using enhanced green fluorescent protein (eGFP) as a benchmark, we demonstrated that the library produced humanized nanobodies with high function and great intracellular stability. The library was then subjected to screening against IL-6. We identified a standout nanobody, NbL3, which exhibited high affinity (22.16 nM) and stability and significantly inhibited IL-6-enhanced migration on the human breast cancer cell MCF-7 at a relatively low concentration. NbL3's strong blocking activity provides a promising therapeutic alternative for the IL-6-targeted intervention strategy, underscoring the broader potential of our synthetic library as a versatile platform for the development of humanized nanobodies against multiple antigens.

Structure-based humanization of a therapeutic antibody for multiple myeloma.

The optimal efficacy of xenogeneically generated proteins intended for application in humans requires that their own antigenicity be minimized. This necessary adaptation of antibodies to a humanized version poses challenges since modifications even distant from the binding sites can greatly influence antigen recognition and this is the primary feature that must be maintained during all modifications. Current strategies often rely on grafting and/or randomization/selection to arrive at a humanized variant retaining the binding properties of the original molecule. However, in terms of speed and efficiency, rationally directed approaches can be superior, provided the requisite structural information is available. We present here a humanization procedure based on the high-resolution X-ray structure of a chimaeric IgG against a marker for multiple myeloma. Based on in silico modelling of humanizing amino acid substitutions identified from sequence alignments, we devised a straightforward cloning procedure to rapidly evaluate the proposed sequence changes. Careful inspection of the structure allowed the identification of a potentially problematic amino acid change that indeed disrupted antigen binding. Subsequent optimization of the antigen binding loop sequences resulted in substantial recovery of binding affinity lost in the completely humanized antibody. X-ray structures of the humanized and optimized variants demonstrate that the antigen binding mode is preserved, with surprisingly few direct contacts to antibody atoms. These results underline the importance of structural information for the efficient optimization of protein therapeutics. KEY MESSAGES: Structure-based humanization of an IgG against BCMA, a marker for Multiple Myeloma. Identification of problematic mutations and unexpected modification sites. Structures of the modified IgG-antigen complexes verified predictions. Provision of humanized high-affinity IgGs against BCMA for therapeutic applications.

Contribution of the abbreviated CAVE-st questionnaire in Spanish: the attitudes toward childbirth experiences.

There are several factors that influence women's childbirth experience, and personal interactions with health professionals are of particular significance. The main objective of this study was to present the validation of an abbreviated form of an existing questionnaire on attitudes about childbirth in medical and nursing students. We used a sample of 512 perinatal medicine and nursing students who received the original 52-item CAVE-st questionnaire to obtain a shorter version with proper psychometric properties. We used Cronbach's alpha coefficient to evaluate the new version's internal consistency. The Kaiser- Meyer-Olkin test and the Barlett sphericity test were performed to assess the suitability of exploratory factor analysis (EFA). Subsequently, confirmatory factor analysis (CFA) was performed using structural equation models in a second sample of 139 medical students. We obtained a 15-item version with a Cronbach's alpha of 0.82. The EFA revealed a four-dimensional structure, similar to the full 52-item version. In the CFA the adjustment indexes showed good model fitness, RMSEA= 0.046 [CI 0.00-0.07]; CFI = 0.978. We can conclude that the 15-item version is a valid tool for evaluating the attitude of students toward childbirth, pointing out the matters that should be improved in their training to avoid obstetric trauma by the promotion of a positive experience in women during childbirth.

Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.

Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines.

Humanization of the antigen-recognition domain does not impinge on the antigen-binding, cytokine secretion, and antitumor reactivity of humanized nanobody-based CD19-redirected CAR-T cells.

BACKGROUND: The immunogenicity of the antigen-recognition domains of chimeric antigen receptor (CAR)-T cells leads to immune responses that may compromise the antitumor effects of the adoptively transferred T cells. Herein, we attempt to humanize a CD19-specific VHH (named H85) using in silico techniques and investigate the impact of antigen-recognition domain humanization on CAR expression and density, cytokine secretion, and cytolytic reactivity of CAR-T cells based on the humanized VHH. METHODS: H85 was humanized (named HuH85), and then HuH85 was compared with H85 in terms of conformational structure, physicochemical properties, antigenicity and immunogenicity, solubility, flexibility, stability, and CD19-binding capacity using in silico techniques. Next, H85CAR-T cells and HuH85CAR-T cells were developed and CAR expression and surface density were assessed via flow cytometry. Ultimately, the antitumor reactivity and secreted levels of IFN-γ, IL-2, and TNF-α were assessed following the co-cultivation of the CAR-T cells with Ramos, Namalwa, and K562 cells. RESULTS: In silico findings demonstrated no negative impacts on HuH85 as a result of humanization. Ultimately, H85CAR and HuH85CAR could be surface-expressed on transduced T cells at comparable levels as assessed via mean fluorescence intensity. Moreover, H85CAR-T cells and HuH85CAR-T cells mediated comparable antitumor effects against Ramos and Namalwa cells and secreted comparable levels of IFN-γ, IL-2, and TNF-α following co-cultivation. CONCLUSION: HuH85 can be used to develop immunotherapeutics against CD19-associated hematologic malignancies. Moreover, HuH85CAR-T cells must be further investigated in vitro and in preclinical xenograft models of CD19+ leukemias and lymphomas before advancing into clinical trials.

macroH2A1 drives nucleosome dephasing and genome instability in histone humanized yeast.

In addition to replicative histones, eukaryotic genomes encode a repertoire of non-replicative variant histones, providing additional layers of structural and epigenetic regulation. Here, we systematically replace individual replicative human histones with non-replicative human variant histones using a histone replacement system in yeast. We show that variants H2A.J, TsH2B, and H3.5 complement their respective replicative counterparts. However, macroH2A1 fails to complement, and its overexpression is toxic in yeast, negatively interacting with yeast's native histones and kinetochore genes. To isolate yeast with macroH2A1 chromatin, we uncouple the effects of its macro and histone fold domains, revealing that both domains suffice to override native nucleosome positioning. Furthermore, both uncoupled constructs of macroH2A1 exhibit lower nucleosome occupancy, decreased short-range chromatin interactions (<20 kb), disrupted centromeric clustering, and increased chromosome instability. Our observations demonstrate that lack of a canonical histone H2A dramatically alters chromatin organization in yeast, leading to genome instability and substantial fitness defects.

Humanization and characterization of an anti-ciguatoxin CTX3C monoclonal antibody.

Ciguatera poisoning (CP), caused by ciguatoxins (CTXs), is one of the most common food-borne diseases, affecting more than 50,000 people each year. In most cases, CP are managed with symptomatic and supportive remedies, and no specific treatment has been devised. In this study, toward the development of therapeutic antibodies for CP, we examined to humanize mouse anti-CTX3C antibody 10C9 (m10C9), which exhibited neutralizing activity against ciguatoxin in vitro and in vivo. The complementarity determining regions were grafted onto a human germline sequence with high sequence identity to m10C9, and the backmutations were examined to maintain the binding affinity. The optimized humanized antibody, Opt.h10C9Fab, showed a strong binding affinity to CTX3C with a high affinity (KD = 19.0 nM), and only two backmutations of ArgL46 and CysH94 in the framework regions were involved in determining the antigen binding affinity.

Single-domain antibodies as therapeutics for solid tumor treatment.

Single-domain antibodies (sdAbs), initially identified in camelids or sharks and commonly referred to as nanobodies or VNARs, have emerged as a promising alternative to conventional therapeutic antibodies. These sdAbs have many superior physicochemical and pharmacological properties, including small size, good solubility and thermostability, easier accessible epitopes, and strong tissue penetration. However, the inherent challenges associated with the animal origin of sdAbs limit their clinical use. In recent years, various innovative humanization technologies, including complementarity-determining region (CDR) grafting or complete engineering of fully human sdAbs, have been developed to mitigate potential immunogenicity issues and enhance their compatibility. This review provides a comprehensive exploration of sdAbs, emphasizing their distinctive features and the progress in humanization methodologies. In addition, we provide an overview of the recent progress in developing drugs and therapeutic strategies based on sdAbs and their potential in solid tumor treatment, such as sdAb-drug conjugates, multispecific sdAbs, sdAb-based delivery systems, and sdAb-based cell therapy.

Comparison of "framework Shuffling" and "CDR Grafting" in humanization of a PD-1 murine antibody.

Introduction: Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans. Methods: Two different strategies of antibody humanization are popularly employed, including "complementarity determining region (CDR) grafting" and "framework (FR) shuffling" to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies. Results: While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background. Discussion: The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field.

Implementation of a routine post-shift debriefing program in ICU aiming at quality-of-care improvement: A primary analysis of feasibility and impacts.

OBJECTIVES: This report describes the implementation of a clinical debriefing (CD) program in intensive care units (ICU) and analyses its feasibility and its impact on staff well-being. DESIGN: Observational study. SETTING: From April to September 2023, post-shift CDs were run once a week in 2 out of 7 units in our department, using an adapted version of the DISCOVER-PHASE tool. CD sessions were performed face-to-face with volunteer members of the multidisciplinary ICU team. MAIN OUTCOME MEASURES: After 6 months, a survey assessing the satisfaction of the debriefed teams was conducted. The impact of CD on staff well-being was assessed using three validated questionnaires (Maslach Burnout Inventory, Ways of Coping Checklist, Professional Quality of Life Scale) administered in the 7 units before and after the CD period. RESULTS: A total of 44 CDs were performed, lasting 15 (4-35) min. There were 6 (1-9) attendees per CD, mainly nurses (64.6%). Discussions focused mainly on basic problems related to dysfunctional material, communication and organization inside the team. The two debriefed teams were satisfied of the program and gave 9, 8 and 8 out of 10 on a visual analogical scale for the climate of confidence of the DC, their organisation, and their ability to improve working conditions and quality of care, respectively. Subscores at the three questionnaires assessing staff well-being before and after the CD period were similar, whether teams experienced CD or not. CONCLUSIONS: Implementing of post-shift debriefings in our ICU was feasible and well accepted. More prolonged programs are probably needed to demonstrate benefits on staff well-being. IMPLICATIONS FOR CLINICAL PRACTICE: This report offers elements that other teams can use to successfully conduct post-shift debriefings and to plan future research on longer-term programs.

Reflexión sobre las ventajas y desventajas de trabajar en un servicio oncológico identificadas por estudiantes de posgrado en oncología, Facultad de Enfermería - Udelar

Desde el año 2017, la Facultad de Enfermería de la Universidad de la República forma licenciados especialistas en enfermería oncológica. Profesionales con competencias específicas para brindar cuidados en relación a la enfermedad asociada a la segunda causa de muerte en Uruguay. Cómo parte del proceso enseñanza-aprendizaje es necesario conocer el perfil de los estudiantes, a través de un sondeo diagnóstico aplicado a la generación en curso (2023/2024) se obtuvo información que da origen a la reflexión desarrollada en el manuscrito a continuación. La percepción de los estudiantes sobre las ventajas y desventajas que implican el ejercicio profesional de enfermería dentro de un servicio de oncología identificadas por los estudiantes. Ventajas que incluyen: aumento de los ingresos económicos, mejor régimen laboral y satisfacción personal. Desventajas que incluyen: desgaste emocional, riesgo ante la exposición a drogas antineoplásicas y riesgo ante el escaso marco normativo frente a la exposición a dichas drogas. Cómo conclusión se considera que la enfermería oncológica es un área que demanda compromiso interpersonal entre los profesionales y el usuario, este compromiso implica esfuerzo pero a su vez empodera los roles y conlleva a la satisfacción personal. A sí mismo, se identifica que es un área poco desarrollada a nivel de reglamentación en relación a la salud ocupacional. El equipo docente además de guiar y acompañar durante el proceso de aprendizaje busca formar profesionales con conciencia crítica capaces de identificar debilidades y amenazas del ejercicio, con la capacidad de generar cambios en pro del avance la de profesión y con ello, el avance de la calidad de atención.

Since 2017, the Faculty of Nursing of the University of the Republic has been training graduates specializing in oncology nursing. Professionals with specific skills to provide care in relation to the disease associated with the second cause of death in Uruguay. As part of the teaching-learning process, it is necessary to know the profile of the students; through a diagnostic survey applied to the current generation (2023/2024), information was obtained that gives rise to the reflection developed in the manuscript below. Students' perception of the advantages and disadvantages of professional nursing practice within an oncology service identified by students. Advantages that include: increased economic income, better work regime and personal satisfaction. Disadvantages that include: emotional exhaustion, risk from exposure to antineoplastic drugs and risk from the scarce regulatory framework against exposure to these drugs. In conclusion, it is considered that oncology nursing is an area that demands interpersonal commitment between professionals and the user. This commitment implies effort but at the same time empowers roles and leads to personal satisfaction. In itself, it is identified that it is an underdeveloped area at the level of regulation in relation to occupational health. The teaching team, in addition to guiding and accompanying during the learning process, seeks to train professionals with critical awareness capable of identifying weaknesses and threats in the practice, with the ability to generate changes in favor of the advancement of the profession and with it, the advancement of quality. of attention.

Desde 2017, a Faculdade de Enfermagem da Universidade da República forma licenciados especializados em enfermagem oncológica. Profissionais com competências específicas para prestar cuidados em relação à doença associada à segunda causa de morte no Uruguai. Como parte do processo de ensino-aprendizagem é necessário conhecer o perfil dos alunos através de um inquérito diagnóstico aplicado à geração atual (2023/2024), foram obtidas informações que dão origem à reflexão desenvolvida no manuscrito abaixo. Percepção dos estudantes sobre as vantagens e desvantagens da prática profissional de enfermagem dentro de um serviço de oncologia identificadas pelos estudantes. Vantagens que incluem: aumento do rendimento económico, melhor regime de trabalho e satisfação pessoal. Desvantagens que incluem: exaustão emocional, risco de exposição a medicamentos antineoplásicos e risco do escasso marco regulatório contra a exposição a esses medicamentos. Concluindo, considera-se que a enfermagem oncológica é uma área que exige comprometimento interpessoal entre profissionais e usuário. Esse comprometimento implica esforço, mas ao mesmo tempo potencializa papéis e leva à satisfação pessoal. Por si só, identifica-se que se trata de uma área subdesenvolvida ao nível da regulação em relação à saúde ocupacional. A equipe docente, além de orientar e acompanhar durante o processo de aprendizagem, busca formar profissionais com consciência crítica capaz de identificar fragilidades e ameaças na prática, com capacidade de gerar mudanças em favor do avanço da profissão e com ela, o avanço da qualidade da atenção.

Humanized oncology nursing care in a person with gastric cancer: A case report.

Cancer impacts the person's physical health, psychosocial and spiritual wellbeing. The humanization of care is an essential element to achieve integral wellbeing of the individual. The aim of this article is to present a clinical case, using the nursing process with the NANDA, NOC and NIC taxonomies, and based on the principles of Watson's theory of humanized care. The participant is a 45-year-old woman with gastric cancer in palliative stage. The assessment was performed using Gordon's functional patterns and the Watson Caritas Patient Score scale to evaluate the care received previously in the health system. Eight nursing diagnoses were identified, prioritizing 3 diagnoses using the clinical reasoning web (decisional conflict, anxiety, and ineffective self-management of health). Expected outcomes and nursing interventions were planned and implemented through moments of care using health education through tele-nursing and the intentional use of Caritas processes of care in the transpersonal relationship. The results were evaluated with the scales of the indicators and anxiety was also evaluated with the Beck Anxiety Inventory. Health education in oncology nursing contributed to improve informed decision making, reducing anxiety and providing emotional support to facilitate self-management of health. The participant perceived as humanized care throughout the sessions, reflected in the final evaluation with the Watson Caritas Patient Score scale.

Debates on humanization of human-animal brain chimeras - are we putting the cart before the horses?

Research on human-animal chimeras have elicited alarms and prompted debates. Those involving the generation of chimeric brains, in which human brain cells become anatomically and functionally intertwined with their animal counterparts in varying ratios, either via xenografts or embryonic co-development, have been considered the most problematic. The moral issues stem from a potential for "humanization" of the animal brain, as well as speculative changes to the host animals' consciousness or sentience, with consequential alteration in the animal hosts' moral status. However, critical background knowledge appears to be missing to resolve these debates. Firstly, there is no consensus on animal sentience vis-à-vis that of humans, and no established methodology that would allow a wholesome and objective assessment of changes in animal sentience resulting from the introduction of human brain cells. Knowledge in interspecies comparative neuropsychology that could allow effective demarcation of a state of "humanization" is also lacking. Secondly, moral status as a philosophical construct has no scientific and objective points of reference. Either changes in sentience or humanization effects would remain unclear unless there are some neuroscientific research grounding. For a bioethical stance based on moral status of human-animal brain chimera to make meaningful contributions to regulatory policies, it might first need to be adequately informed by, and with its arguments constructed, in a manner that are factually in line with the science. In may be prudent for approved research projects involving the generation of human-animal brain chimera to have a mandatory component of assessing plausible changes in sentience.

Eating pigs, not Peppa Pig: The effect of identifiability on children's propensity to humanize, befriend, and consume edible animals.

This research aimed to provide experimental evidence on whether identifying an edible animal by a name and specific preferences encourages children to perceive the animal as more similar to humans, increases their willingness to befriend the animal, and makes them less willing to consume it. In two pre-registered studies involving 208 preschool children, participants were presented with pictures of pigs (Study 1) and chickens (Study 2). In the identifiability condition, one animal was depicted with individual qualities such as a name and personal preferences, while in the non-identifiability condition, animals were portrayed with characteristics representative of the entire species. The children then rated their desire to befriend and consume the animal, while in Study 2, they also rated the animal's similarity to humans. The results revealed that animal identifiability led to higher perceived similarity to humans, increased the desire to befriend it, and reduced inclination to consume the animal. These findings highlight animal identifiability's powerful and robust effect on children's attitudes toward edible animals.

Prospects for the computational humanization of antibodies and nanobodies.

To be viable therapeutics, antibodies must be tolerated by the human immune system. Rational approaches to reduce the risk of unwanted immunogenicity involve maximizing the 'humanness' of the candidate drug. However, despite the emergence of new discovery technologies, many of which start from entirely human gene fragments, most antibody therapeutics continue to be derived from non-human sources with concomitant humanization to increase their human compatibility. Early experimental humanization strategies that focus on CDR loop grafting onto human frameworks have been critical to the dominance of this discovery route but do not consider the context of each antibody sequence, impacting their success rate. Other challenges include the simultaneous optimization of other drug-like properties alongside humanness and the humanization of fundamentally non-human modalities such as nanobodies. Significant efforts have been made to develop in silico methodologies able to address these issues, most recently incorporating machine learning techniques. Here, we outline these recent advancements in antibody and nanobody humanization, focusing on computational strategies that make use of the increasing volume of sequence and structural data available and the validation of these tools. We highlight that structural distinctions between antibodies and nanobodies make the application of antibody-focused in silico tools to nanobody humanization non-trivial. Furthermore, we discuss the effects of humanizing mutations on other essential drug-like properties such as binding affinity and developability, and methods that aim to tackle this multi-parameter optimization problem.

Preclinical development of humanized monoclonal antibodies against CD169 as a broad antiviral therapeutic strategy.

New therapies to treat or prevent viral infections are essential, as recently observed during the COVID-19 pandemic. Here, we propose a therapeutic strategy based on monoclonal antibodies that block the specific interaction between the host receptor Siglec-1/CD169 and gangliosides embedded in the viral envelope. Antibodies are an excellent option for treating infectious diseases based on their high specificity, strong targeting affinity, and relatively low toxicity. Through a process of humanization, we optimized monoclonal antibodies to eliminate sequence liabilities and performed biophysical characterization. We demonstrated that they maintain their ability to block viral entry into myeloid cells. These molecular improvements during the discovery stage are key if we are to maximize efforts to develop new therapeutic strategies. Humanized monoclonal antibodies targeting CD169 provide new opportunities in the treatment of infections caused by ganglioside-containing enveloped viruses, which pose a constant threat to human health. In contrast with current neutralizing antibodies that bind antigens on the infectious particle, our antibodies can prevent several types of enveloped viruses interacting with host cells because they target the host CD169 protein, thus becoming a potential pan-antiviral therapy.