- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- TGF-β signaling in diseases
- Immunotherapy and Immune Responses
- Connective tissue disorders research
- Lymphoma Diagnosis and Treatment
- Biochemical and Structural Characterization
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
- Immune Cell Function and Interaction
- Bone health and treatments
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Hematopoietic Stem Cell Transplantation
- Bone Metabolism and Diseases
- Viral Infections and Immunology Research
- Cancer Cells and Metastasis
- Heterotopic Ossification and Related Conditions
- Periodontal Regeneration and Treatments
- Pneumonia and Respiratory Infections
- Viral gastroenteritis research and epidemiology
- Platelet Disorders and Treatments
AIMM Therapeutics (Netherlands)
2012-2021
Amsterdam UMC Location University of Amsterdam
2013-2017
B cell chronic lymphocytic leukemia (CLL), the most common in adults, is a clonal expansion of CD5+CD19+ lymphocytes. Two types CLLs are being distinguished as carrying either unmutated or somatically mutated immunoglobulins (Igs), which associated with unfavorable and favorable prognoses, respectively. More than 30% can be grouped based on their expression stereotypic receptors (BCRs), strongly suggesting that distinctive antigens involved development CLL. Unmutated CLLs, Ig heavy chain...
Genetically encoded tyrosine (Y-tag) can be utilized as a latent anchor for inducible and site-selective conjugation. Upon oxidation of with mushroom tyrosinase, strain-promoted cycloaddition (SPOCQ) the resulting 1,2-quinone various bicyclo[6.1.0]nonyne (BCN) derivatives led to efficient The method was applied fluorophore labeling laminarinase A site-specific preparation an antibody–drug conjugate.
Significance Bispecific antibodies expand the function of conventional antibodies. However, therapeutic application bispecifics is hampered by reduced physiochemical stability such molecules. We present a format for bispecific antibodies, fusing two full-sized via their C termini. This does not require mutations in antibody constant domains beyond installation five-residue tag, ensuring that native structure fully retained product. have validated approach linking anti-influenza A each active...
ABSTRACT Respiratory syncytial virus (RSV) causes severe respiratory disease in young children. Antibodies specific for the RSV prefusion F protein have guided vaccine research, and human serum, these antibodies contribute to >90% of neutralization response; however, detailed insight into composition B cell repertoire against is still largely unknown. In order study three healthy donors specificity RSV, CD27 + memory cells were isolated immortalized using BCL6 Bcl-xL. Of circulating...
Generation of effective immune responses requires expansion rare antigen-specific CD4(+) T cells. The magnitude the responding population is ultimately determined by proliferation and survival. Both processes are tightly controlled to limit innocuous antigens. Sustained occurs only when innate sensors activated microbial stimuli or adjuvants, which has important implications for vaccination. molecular identity signals controlling sustained T-cell not fully clear. Here, we describe a...
Hepatitis C virus (HCV) is world-wide a major cause of liver related morbidity and mortality. No vaccine available to prevent HCV infection. To design an effective vaccine, understanding immunity against necessary. The memory B cell repertoire was characterized from intravenous drug user who spontaneously cleared infection 25 years ago. CD27+IgG+ cells were immortalized using BCL6 Bcl-xL. These used study antibody-mediated the E1E2 glycoproteins. Five broadly reactive antibodies isolated: 3...
Objective Patients with Sjӧgren's syndrome ( SS ) have an increased risk of developing malignant B cell lymphomas, particularly mucosa‐associated lymphoid tissue MALT )–type lymphomas. We previously shown that a predominant proportion patients ‐associated salivary gland lymphoma express somatically hypermutated IgM strong amino acid sequence homology stereotypic rheumatoid factors RF s). The present study was undertaken in larger cohort to more firmly assess the frequency reactivity and...
ABSTRACT Since it was first recognized in 2004 that human parechoviruses (HPeV) are a significant cause of central nervous system and neonatal sepsis, their clinical importance, primarily children, has started to emerge. Intravenous immunoglobulin treatment is the only available such life-threatening cases given moderate success. Direct inhibition parechovirus infection using monoclonal antibodies potential treatment. We have developed two neutralizing against HPeV1 HPeV2, namely, AM18 AM28,...
Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage tumor-immunotherapeutic effect allogeneic hematopoietic stem cell transplantation searched B-cell repertoire a patient with lasting potent graft-versus-AML response presence AML-specific antibodies. identified an antibody, AT1413, that was donor origin...
In prospect of developing an oral dosage form Infliximab, for treatment Crohn's disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) spray-drying were investigated as production method stable powders. Dextran inulin used in combination with sucrose stabilizing excipients. The drying processes did not affect Infliximab these formulations, i.e. both the physical integrity biological activity (TNF binding) retained. Accelerated stability studies (1 month at 60°C) showed that...
The family Picornaviridae is a large and diverse group of positive-sense RNA viruses, including human enteroviruses (EVs) parechoviruses (HPeVs). immune response against EVs HPeVs thought to be mainly humoral, an insufficient neutralizing antibody (Ab) during infection risk factor can ultimately life threatening. accessibility different antigenic sites observed cross-reactivity make good target for development therapeutic monoclonal antibodies (MAbs). In this study, we generated two MAbs...
Knob-in-hole antibodies can be utilized to introduce a single tag for chemo-enzymatic functionalization. By either introducing C-terminal sortase (sortase-tag expressed protein ligation) or tyrosine (G4Y), mono-functionalization of the monoclonal antibody trastuzumab was achieved rapidly and in high yields. This method applied selectively efficiently fluorescent tag, cytokine single-chain variable fragment, as well produce clean homo dimers trastuzumab.
Abstract Bone morphogenetic proteins (BMP) have important but distinct roles in tissue homeostasis and disease, including carcinogenesis tumor progression. A large number of BMP inhibitors are available to study function; however, as most these antagonists promiscuous, evaluating specific effects individual BMPs is not feasible. Because the oncogenic role different varies for each neoplasm, highly selective required. Here, we describe generation three types llama-derived heavy chain variable...
Acute myeloid leukemia (AML) is a high-risk disease with poor prognosis, particularly in elderly patients. Because current AML treatment relies primarily on untargeted therapies severe side effects that limit patient eligibility, identification of novel therapeutic targets highly desired. We recently described AT1413, an antibody produced by donor B cells cured after allogeneic hematopoietic stem cell transplantation. AT1413 binds CD43s, unique sialylated epitope CD43, which weakly expressed...
Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) can cure acute myeloid leukemia (AML) when the donor immune system generates a potent graft versus (GvL) response. While role of T cells and NK in GvL responses has been established, contribution B to is less clear. Using SEREX other techniques, presence antibodies directed against established tumor antigens following allogeneic HSCT demonstrated, but because these were not obtained monoclonal format, function...
One-third of chronic lymphocytic leukemias (CLL) can be grouped into stereotyped B-cell receptor (BCR) subsets based on similarity their expressed variable heavy chain complementarity-determining regions 3 (VH-CDR3).1 Previously, we and Kostareli et al identified 2 novel CLL with somatically mutated immunoglobulin region (IGHV), each representing 0.2% CLL, expressing IGHV3-7-encoded IGHV4-59-encoded rheumatoid factors (RFs).2,3 Interestingly, stereotypic V4-59-RFs are identical to BCR subset...
<div>Abstract<p>Bone morphogenetic proteins (BMP) have important but distinct roles in tissue homeostasis and disease, including carcinogenesis tumor progression. A large number of BMP inhibitors are available to study function; however, as most these antagonists promiscuous, evaluating specific effects individual BMPs is not feasible. Because the oncogenic role different varies for each neoplasm, highly selective required. Here, we describe generation three types llama-derived...