Carl A K Borrebaeck

Lund University | LU · Department of Immunotechnology

Purpose Improved early diagnosis and determination of aggressiveness of prostate cancer (PC) is important to select suitable treatment options and to decrease over‐treatment. The conventional marker is total prostate specific antigen (PSA) levels in blood, but lacks specificity and ability to accurately discriminate indolent from aggressive disease...

Fluorescence-based detection assays play an essential role in the life sciences and medicine. To offer better detection sensitivity and lower limits of detection (LOD), there is a growing need for novel platforms with an improved readout capacity. In this context, substrates containing semiconductor nanowires may offer significant advantages, due t...

Background Standard biopsy for prostate cancer diagnosis is an unpleasant and sometimes painful procedure with a detection rate as low as around 50%. Consequently, an accurate blood-based test would be highly desirable to improve the predictive accuracy. However, the clinical value of a new blood test for diagnosing prostate cancer depends on its s...

The composition of serum proteins is reflecting the current health status and can, with the right tools, be used to detect early signs of disease, such as an emerging cancer. An earlier diagnosis of cancer would greatly increase the chance of an improved outcome for the patients. However, there is still an unmet need for proficient tools to deciphe...

Background: The Connor-Davidson Resilience Scale (CD-RISC) is the most widely used scale which assesses psychological resilience. Although it is recommended to be applied as a unidimensional scale, its factor structure, reliability, as well as discriminant and predictive validity need to be assessed when used in a new context. Moreover, the origin...

Purpose Psychological resilience appears to be an important influencing factor in various aspects of health-related quality of life (HRQoL) in a context of adversity, e.g., being informed of a cancer diagnosis. The purpose was to investigate psychological resilience and health-related quality of life in Swedish women with newly diagnosed breast can...

There is an increasing demand for alternative in vitro methods to replace animal testing, and, to succeed, new methods are required to be at least as accurate as existing in vivo tests. However, skin sensitization is a complex process requiring coordinated and tightly regulated interactions between a variety of cells and molecules. Consequently, th...

Purpose: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of < 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signatur...

Background: Individual patients differ in their psychological response when receiving a cancer diagnosis, in this case breast cancer. Given the same disease burden, some patients master the situation well, while others experience a great deal of stress, depression and lowered quality of life. Patients with high psychological resilience are likely...

Surface display couples genotype with a surface exposed phenotype and thereby allows screening of gene-encoded protein libraries for desired characteristics. Of the various display systems available, phage display is by far the most popular, mainly thanks to its ability to harbour large size libraries. Here, we describe the first use of a Gram-posi...

Histological grade is one of the most commonly used prognostic factors for patients diagnosed with breast cancer. However, conventional grading has proven technically challenging, and up to 60% of the tumors are classified as histological grade 2, which represents a heterogeneous cohort less informative for clinical decision making. In an attempt t...

Raw antibody microarray data. The observed array signal intensity for each antibody is listed per sample. (XLSX)

Genomic allergen rapid detection (GARD) is an in vitro assay for the prediction of skin sensitizing capacity of chemicals. The GARD assay monitors changes in the expression of 196 genes, termed the GARD prediction signature. In short, MUTZ-3 cells, representing a well-characterized in vitro model of human dendritic cells (DCs), are exposed to the t...

Interest in precision diagnostics has been fuelled by the concept that early detection of cancer would benefit patients; that is, if detected early, more tumours should be resectable and treatment more efficacious. Serum contains massive amounts of potentially diagnostic information, and affinity proteomics has risen as an accurate approach to deci...

Alternative methods for accurate in vitro assessment of skin and respiratory sensitizers are urgently needed. Sensitization is a complex biological process that cannot be evaluated accurately using single events or biomarkers, since the information content is too restricted in these measurements. On the contrary, if the tremendous information conte...

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma. The disease is heterogeneous with respect to the clinical course and molecular findings, making the management of these patients challenging. Deepened understanding of DLBCL pathogenesis has opened novel possibilities for early patient prognostication, but a furth...

Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, whi...

Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed...

In the quest for deciphering disease-associated biomarkers, high-performing tools for multiplexed protein expression profiling of crude clinical samples will be crucial. Affinity proteomics, mainly represented by antibody-based microarrays, have during recent years been established as a proteomic tool providing unique opportunities for parallelized...

Evaluation of different normalization procedures. MeanSdPlots were used as qualitative measures in order to compare the log intensity distribution of samples output with respect to log2 transformed data, Local LOESS, Local VSN, Global LOESS, Global VSN and Quantile normalizations. (EPS)

Schematic outline of how methods for defining a condensed biomarker signature were evaluated. The data set, composed of two groups–healthy (H) and disease (D)—was randomly divided in two three subsets. Condensed biomarker signatures of a fixed length (N = 25) of the top-ranked biomarkers were defined using each of the feature selection methods (p-v...

Evaluation of different normalization procedures. Density plots were used as qualitative measures in order to compare the log intensity distribution of samples output with respect to log2 transformed data, Local LOESS, Local VSN, Global LOESS, Global VSN and Quantile normalizations. (EPS)

Evaluation of different normalization procedures. Boxplots were used as qualitative measures in order to compare the log intensity distribution of samples output with respect to log2 transformed data, Local LOESS, Local VSN, Global LOESS, Global VSN and Quantile normalizations. (EPS)

Antigens targeted on the antibody microarray. The specificity, affinity (normally in the nM range), and on-chip functionality of all of these phage display derived scFv antibodies were ensured by using i) stringent phage-display selection and screening protocols (using different sample formats, ranging from pure proteins and mixtures of pure protei...

Evaluation of different normalization processes. To this end, microarray data for diseased group 3 vs. group 1 samples was used and compared with respect to No. of down-regulated scFvs antibodies and No. of complete matches per target molecule, using a fold change (FC) filter of FC > 1. (DOCX)

Top 50 differentially expressed proteins (represented by their matching antibody clone) for diseased vs healthy controls, before and after normalization. (DOCX)

Effect of the Combat plus semi-global normalization on the sample variability. The sample cohort included QCref samples as well as diseased and healthy samples. i) QCref samples analyzed on two days. ii) Diseased vs. healthy samples analyzed on different days (mapped for day). iii) Diseased vs. healthy samples analyzed on different days (mapped for...

Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according...

Antibody microarrays have emerged as an important tool within proteomics, enabling multiplexed protein expression profiling in both health and disease. The design and performance of antibody microarrays and how they are processed are dependent on several factors, of which the interplay between the antibodies and the solid surfaces plays a central r...

Increasing the understanding of a proteome and how its protein composition is affected by for example different diseases, such as cancer, has the potential to improve strategies for early diagnosis and therapeutics. The Global Proteome Survey or GPS is a method that combines mass spectrometry and affinity enrichment with the use of antibodies. The...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sa...

Supplementary Figure 1: Slide and microarray lay-out. Supplementary Figure 2: Data visualized by principal component analysis. Supplementary Figure 3: Biomarker assessment by database queries for diseases by biomarkers. Supplementary Table 1: Antigens targeted on the antibody microarray. Supplementary Table 2: Context-independent motif specific ant...

Interview with Professor Carl Borrebaeck DSc by Claire Raison (Commissioning Editor) Professor Carl Borrebaeck DSc, is the Director of CREATE Health (Lund, Sweden), a translational cancer center, previous Vice President of Lund University and specializes in immunotechnology, diagnostics and treatments for cancer. He has had remarkable success in co...

Antibody-based microarray is a recently established proteomic technology, providing unique opportunities for multiplexed protein expression profiling of crude, non-fractionated samples in a specific, sensitive and miniaturised manner. A microarray can be printed with a few up to several thousands of different antibodies carrying the desired specifi...

Repeated exposure to certain low molecular weight (LMW) chemical compounds may result in development of allergic reactions in the skin or in the respiratory tract. In most cases, a certain LMW compound selectively sensitize the skin, giving rise to allergic contact dermatitis (ACD), or the respiratory tract, giving rise to occupational asthma (OA)....

Background Despite recent advances in molecular profiling of diffuse large B-cell lymphoma (DLBCL), only a few biomarkers currently have an impact on treatment. In a previous study we could observe the heterogeneity of DLBCL in the plasma immunoprofile from DLBCL patients, by use of recombinant antibody microarrays. By unsupervised hierarchical clu...

Purpose: Early detection of prostate cancer (PC) using prostate-specific antigen (PSA) in blood reduces PC-death among unscreened men. However, due to modest specificity of PSA at commonly used cut-offs, there are urgent needs for additional biomarkers contributing enhanced risk classification among men with modestly elevated PSA. Experimental de...

The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, i...

The ability to design and tailor-make antibodies to meet the biophysical demands required by the vast range of current and future antibody-based applications within biotechnology and biomedicine will be essential. In this proof-of-concept study, we have for the first time tailored human recombinant scFv antibodies for site-specific photocoupling th...

The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145...

Miniaturized (Ø 10 μm), multiplexed (>5-plex), and high-density (>100 000 spots cm(-2)) antibody arrays will play a key role in generating protein expression profiles in health and disease. However, producing such antibody arrays is challenging, and it is the type and range of available spotters which set the stage. This pilot study explored the us...

Background: Antibody-based microarrays are a developing tool for high-throughput proteomics in health and disease. However, in order to enable global proteome profiling, novel miniaturized high-density antibody array formats must be developed. Results: In this proof-of-concept study, we have designed a miniaturized planar recombinant (single-cha...

In the quest to decipher disease-associated biomarkers, miniaturized and multiplexed antibody arrays may play a central role in generating protein expression profiles, or protein maps, of crude serum samples. In this conceptual study, we explored a novel, 4-times larger pen design, enabling us to, in a unique manner, simultaneously print 48 differe...

Chemical sensitization is an adverse immunologic response to chemical substances, inducing hypersensitivity in exposed individuals. Identifying chemical sensitizers is of great importance for chemical, pharmaceutical and cosmetic industry, in order to prevent the use of sensitizers in consumer products. Historically, chemical sensitizers have been...

B-cell lymphoma (BCL) heterogeneity represents a key issue, often making the classification and clinical management of these patients challenging. In this pilot study, we outlined the first resolved view of BCL disease heterogeneity on the protein level by deciphering disease-associated plasma biomarkers, specific for chronic lymphocytic leukemia,...

Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify ch...

Affinity proteomics, represented by antibody arrays, is a multiplex technology for high-throughput protein expression profiling of crude proteomes in a highly specific, sensitive, and miniaturized manner. The antibodies are individually deposited in an ordered pattern, an array, onto a solid support. Next, the sample is added, and any specifically...

Systemic lupus erythematosus (SLE) is a severe autoimmune connective tissue disease. Our current knowledge about the serum proteome, or serum biomarker panels, reflecting disease and disease status is still very limited. Affinity proteomics, represented by recombinant antibody arrays, is a novel, multiplex technology for high-throughput protein exp...

Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully eva...

Agonistic antibodies targeting costimulatory pathways for the immune system hold great potential for cancer immunotherapy. However, systemic administration of immunoactivating antibodies can be associated with side effects such as cytokine release syndrome and liver toxicity. Polymeric nanoparticles (NPs) represent an exciting approach to control t...

Proteomics, the large-scale analysis of proteins, is a rapidly evolving field with an increasing number of key clinical applications, such as diagnosis, prognosis, and classification. In order to generate complete protein expression profiles, or protein atlases, any crude sample format must be addressable in a rapid, multiplex, and sensitive manner...

Tumor progression and prognosis of breast cancer patients is difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessment of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with h...

T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in hum...

Clinicopathological characteristics of the patients. (DOCX)

Protein-peptide interactions are a common occurrence and essential for numerous cellular processes, and frequently explored in broad applications within biology, medicine, and proteomics. Therefore, understanding the molecular mechanism(s) of protein-peptide recognition, specificity, and binding interactions will be essential. In this study, we rep...

Pancreatitis is an inflammatory state of the pancreas, for which high-performing serological biomarkers are lacking. The aim of the present study was to evaluate the use of affinity proteomics for identifying potential markers of disease and stratifying pancreatitis subtypes. High-content, recombinant antibody microarrays were applied for serum pro...

Allergic contact dermatitis is a skin disease caused by an immunologic reaction to low molecular weight compounds, so called haptens. These substances are commonly present in products used by humans in daily life, such as in cosmetics and fragrances, as well as within chemical industry and in pharmaceuticals. The frequent usage of these compounds i...

Despite massive efforts, proteomics has not delivered biomarkers of clinical value. However, the technologies that are emerging today have the power to reach deep into proteomes and identify the patterns associated with different diseases. Study design is then crucial and sample quality, bioinformatics approaches, prevalidation, using independent p...

Background The transcription factor SOX11 is of diagnostic and prognostic importance in mantle cell lymphoma (MCL) and epithelial ovarian cancer (EOC), respectively. Thus, there is an unmet clinical and experimental need for SOX11-targeting assays with low background, high specificity and robust performance in multiple applications, including immun...

Agonistic anti-CD40 monoclonal antibodies (mAbs) hold great potential for cancer immunotherapy. However, systemic administration of anti-CD40 mAbs can be associated with severe side effects, such as cytokine release syndrome and liver damage. With the aim to increase the immunostimulatory potency as well as to achieve a local drug retention of anti...

Urinary proteomics has become a key discipline within clinical proteomics for noninvasive diagnosis and monitoring of disease, and biomarker discovery. In order to decipher complex proteomes, high demands will, however, be placed upon the methodology applied. The purpose of this study was to develop a recombinant antibody microarray platform for ur...

Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimm...

The development of high-performance technology platforms for generating detailed protein expression profiles, or protein atlases, is essential. Recently, we presented a novel platform that we termed global proteome survey, where we combined the best features of affinity proteomics and mass spectrometry, to probe any proteome in a species independen...

The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs ma...

The transcription factor SOX11 is a novel diagnostic marker for mantle cell lymphoma (MCL), distinguishing this aggressive tumor from potential simulators. Recent data also show that the level of SOX11 correlates to in vitro growth properties in MCL, as well as the clinical progression. We have previously shown that MCL-associated pathways, such as...

The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera fro...