Antibody Engineering and Immune System
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Questions and Answers

What is the typical size of the antibody repertoire obtained from human donors?

  • 10^11 CFU
  • 10^9 CFU (correct)
  • 10^7 CFU
  • 10^10 CFU
  • What is the mechanism of action of Ofatumumab in killing tumor cells?

  • It binds to the large loop epitope of CD20
  • It activates granzymes and cytokines to induce apoptosis
  • It generates high avidity C1q binding and efficient C3b deposition (correct)
  • It induces FcgR upregulation and attracts effector cells
  • What is the purpose of the Mammalian Display Platform?

  • To optimize antibody potency
  • To increase antibody diversity
  • To select antibodies for developability (correct)
  • To improve antibody affinity
  • What is the characteristic of Ofatumumab that makes it more effective in vitro CDC compared to Rituximab?

    <p>It binds to a novel small loop epitope of CD20</p> Signup and view all the answers

    What is the name of the company that provides antibody technologies for drug candidate development?

    <p>FairJourney Biologics</p> Signup and view all the answers

    What is the indication for which Ofatumumab was first approved by the FDA?

    <p>Chronic lymphocytic leukemia</p> Signup and view all the answers

    What is the name of the antibody that activates gdT cells in immuno-oncology?

    <p>Anti-BTN3A Ab</p> Signup and view all the answers

    What is the purpose of the 'Explorer' platform in antibody discovery?

    <p>To semi-synthetically design diverse repertoires</p> Signup and view all the answers

    What is the brand name of the Ofatumumab product approved by the FDA and EMA?

    <p>Arzerra</p> Signup and view all the answers

    What is the advantage of Ofatumumab in depleting B cells and tumor cells in in vivo models?

    <p>It is relatively insensitive to complement regulatory factors</p> Signup and view all the answers

    What is the name of the publication that describes the Mammalian Display Platform?

    <p>Parthiban et al. (2019), Mabs: 11(5): 884-898</p> Signup and view all the answers

    What is the format of Ofatumumab?

    <p>Humanized IgG1</p> Signup and view all the answers

    What is the challenge mentioned in the given text?

    <p>Large library with 1 gene/cell</p> Signup and view all the answers

    What is the benefit of using Mammalian Display?

    <p>Selection of clones with optimal biophysical properties</p> Signup and view all the answers

    What was the outcome of the affinity maturation of Bococizumab using Phage Display?

    <p>Multiple developability “red flags”</p> Signup and view all the answers

    What was the problem with Bococizumab in the phase 3 clinical trial?

    <p>High immunogenicity</p> Signup and view all the answers

    What is the goal of using Mammalian Display for Bococizumab?

    <p>To fix its developability properties</p> Signup and view all the answers

    What was the outcome of the Safety Review Committee's evaluation of ICT01 in the EVICTION Cohort 1?

    <p>Dose escalation to Cohort 3</p> Signup and view all the answers

    What was observed in the tumor biopsies of the Melanoma patient after ICT01 treatment?

    <p>An increase in tumor infiltrating gd T cells, CD3, CD4 and CD8 T cells</p> Signup and view all the answers

    What is the goal of the New (Antibody) Drug Discovery Unit at the University of Maastricht?

    <p>To bridge the gap between new targets and new biologics drugs for patients</p> Signup and view all the answers

    What was the outcome of ICT01 treatment in the Melanoma patient?

    <p>An increase in gd T cells and CD3+ T cells</p> Signup and view all the answers

    What was the safety profile of ICT01 in the EVICTION Cohort 1?

    <p>Had a good safety profile with no DLTs or related SAEs</p> Signup and view all the answers

    What was the effect of ICT01 on gd T cells in the EVICTION Cohort 1?

    <p>Specifically activated gd T cells after each dose</p> Signup and view all the answers

    What is the primary focus of antibody engineering in relation to the target?

    <p>Achieving antibody diversity to the target</p> Signup and view all the answers

    What is the purpose of glycosylation in human IgG?

    <p>Increasing therapeutic efficacy</p> Signup and view all the answers

    What is the characteristic of chimeric, humanized, and human antibodies?

    <p>Only CDRs are murine</p> Signup and view all the answers

    What is the main difference between in vitro and in vivo technologies in antibody lead discovery?

    <p>In vitro technology uses mammalian display</p> Signup and view all the answers

    What is the region of an antibody responsible for its specificity and affinity?

    <p>CDR loops</p> Signup and view all the answers

    What is the result of somatic mutations in antibody engineering?

    <p>Enhanced antibody diversity</p> Signup and view all the answers

    What is the primary focus of René Hoet's lecture in GEN3505/2024?

    <p>Discussing the discovery and optimization of therapeutic antibodies</p> Signup and view all the answers

    What is the primary method of antibody discovery used in the case study of FXIa Ab?

    <p>Phage display</p> Signup and view all the answers

    What is the title of the course where René Hoet's lecture is being held?

    <p>Engineering the Immune System</p> Signup and view all the answers

    Which immune cells are specifically targeted by BTN3A?

    <p>gd T-cells under stress</p> Signup and view all the answers

    What is the focus of the next generation of immuno-oncology?

    <p>Activating gdT cells with anti-BTN3A antibodies</p> Signup and view all the answers

    What is the expression profile of BTN3A across various types of cancer?

    <p>Over-expressed in solid tumors and down-regulated in blood cancers</p> Signup and view all the answers

    What is the name of the company where René Hoet holds the position of Chief Innovation Officer?

    <p>FairJourney Biologics</p> Signup and view all the answers

    What is the outcome of ICT01-mediated indirect activation on endogenous gd T cells?

    <p>Stimulation of stress-induced phosphoantigen production</p> Signup and view all the answers

    What is the name of the antibody that is mentioned in the case study for migraine treatment?

    <p>CGRP</p> Signup and view all the answers

    What is the theme of René Hoet's lecture, as indicated by the keyword 'synergy'?

    <p>Team effort in building effective antibody products</p> Signup and view all the answers

    What is the technology used by FairJourney Biologics for antibody discovery?

    <p>Mammalian Display Technology</p> Signup and view all the answers

    What is the date of René Hoet's lecture in GEN3505/2024?

    <p>March 12, 2024</p> Signup and view all the answers

    What is the context in which BTN3A is involved in the activation of gd T cells?

    <p>Immune-oncology</p> Signup and view all the answers

    What is the name of the company that developed the antibody Ofatumumab?

    <p>Genmab</p> Signup and view all the answers

    What is the expression pattern of BTN3A in pancreatic tissues?

    <p>Differentially expressed in normal and pancreatic ductal adenocarcinoma</p> Signup and view all the answers

    What is the topic of one of the case studies discussed in René Hoet's lecture?

    <p>FXIa Ab development using phage display</p> Signup and view all the answers

    What is the purpose of screening pancreatic tissues with several BTN3A mAbs?

    <p>To identify the most effective mAb for cancer therapy</p> Signup and view all the answers

    What is the challenge mentioned in the text for therapeutic antibodies?

    <p>The high hanging fruit</p> Signup and view all the answers

    What is the primary mechanism of action of Ofatumumab in killing tumor cells?

    <p>Complement-Dependent Cytotoxicity (CDC)</p> Signup and view all the answers

    What is unique about the epitope of Ofatumumab compared to Rituximab?

    <p>It binds to a novel small loop epitope</p> Signup and view all the answers

    What is the format of the CD20 monoclonal antibody, Ofatumumab?

    <p>Humanized IgG1</p> Signup and view all the answers

    What is the indication for which Ofatumumab was first approved by the FDA and EMA?

    <p>Chronic Lymphocytic Leukemia (CLL)</p> Signup and view all the answers

    What is the characteristic of Ofatumumab that makes it more effective in vitro CDC compared to Rituximab?

    <p>It binds to a novel small loop epitope</p> Signup and view all the answers

    What is the advantage of Ofatumumab in depleting B cells and tumor cells in in vivo models?

    <p>It is more effective at low CD20 expression</p> Signup and view all the answers

    What is the primary outcome of the EVICTION Cohort 1 in relation to gd T cells and CD3+ T cells?

    <p>Increase of gd T cells and CD3+ T cells infiltration</p> Signup and view all the answers

    What is the purpose of the New (Antibody) Drug Discovery Unit at the University of Maastricht?

    <p>To bridge the gap between new targets and new biologics</p> Signup and view all the answers

    What is the characteristic of ICT01 in the EVICTION Cohort 1?

    <p>It has a good safety profile</p> Signup and view all the answers

    What is the outcome of the Safety Review Committee's evaluation of ICT01 in the EVICTION Cohort 1?

    <p>Dose escalation approval</p> Signup and view all the answers

    What is the effect of ICT01 on gd T cells in the EVICTION Cohort 1?

    <p>Specific activation of gd T cells</p> Signup and view all the answers

    What is the observation in the tumor biopsies of the Melanoma patient after ICT01 treatment?

    <p>Increase in tumor-infiltrating gd T cells, CD3, CD4, and CD8 T cells</p> Signup and view all the answers

    What is the primary goal of René Hoet's lecture in GEN3505/2024?

    <p>To introduce the concept of antibody lead discovery and optimization</p> Signup and view all the answers

    Which of the following is NOT a case study discussed in René Hoet's lecture?

    <p>Rituximab (Roche, hybridoma technology)</p> Signup and view all the answers

    What is the title of the course where René Hoet's lecture is being held?

    <p>Engineering the Immune System</p> Signup and view all the answers

    What is René Hoet's position at the University of Maastricht?

    <p>Lecturer in Biopharmaceutics</p> Signup and view all the answers

    What is the company where René Hoet holds the position of Chief Innovation Officer?

    <p>FairJourney Biologics</p> Signup and view all the answers

    What is the focus of the next generation of immuno-oncology according to René Hoet's lecture?

    <p>CGRP (Migraine) antibodies</p> Signup and view all the answers

    What is the primary factor that contributes to the diversity of antibody combinations?

    <p>Combinatorial diversity of V, D, and J segments</p> Signup and view all the answers

    What is the purpose of glycosylation in human IgG?

    <p>Improved therapeutic efficacy</p> Signup and view all the answers

    What is the characteristic of humanized antibodies that reduces their immunogenicity?

    <p>Absence of murine CDRs</p> Signup and view all the answers

    What is the primary goal of in vitro antibody lead discovery technologies?

    <p>To generate antibodies with high diversity</p> Signup and view all the answers

    What is the region of an antibody responsible for its specificity and affinity?

    <p>CDR loops</p> Signup and view all the answers

    What is the primary advantage of using Mammalian Display technology in antibody lead discovery?

    <p>Improved antibody diversity</p> Signup and view all the answers

    What is the primary mechanism by which BTN3A induces the activation of gd T cells?

    <p>Inducing phosphoantigen production under stress</p> Signup and view all the answers

    What is the purpose of screening pancreatic tissues with multiple BTN3A mAbs?

    <p>To study the expression profile of BTN3A in pancreatic tissues</p> Signup and view all the answers

    What is the outcome of ICT01-mediated indirect activation on endogenous gd T cells?

    <p>Activation of gd T cells under stress</p> Signup and view all the answers

    What is the characteristic of BTN3A expression across various types of cancer?

    <p>Differential expression in solid tumors and blood cancers</p> Signup and view all the answers

    What is the role of BTN3A in the context of gd T cell activation?

    <p>Inducing gd T cell activation in response to phosphoantigens</p> Signup and view all the answers

    What is the primary focus of the ICT01 antibody in the context of immuno-oncology?

    <p>Activating gd T cells in solid tumors</p> Signup and view all the answers

    What is the primary mechanism by which Ofatumumab kills resistant tumor cells?

    <p>By ADCC and CDC</p> Signup and view all the answers

    What is the characteristic of Ofatumumab that makes it more effective in vitro CDC compared to Rituximab?

    <p>More efficient complement-dependent cytotoxicity</p> Signup and view all the answers

    What is the significance of the expression of CD20 on the surface of tumor cells in relation to Ofatumumab?

    <p>It is the target antigen for Ofatumumab</p> Signup and view all the answers

    What is the implication of the data showing that Ofatumumab is effective in killing tumor cells with low CD20 expression?

    <p>It implies that Ofatumumab can be used to target a broader range of tumor cells</p> Signup and view all the answers

    What is the significance of the comparison of Ofatumumab and Rituximab in terms of CDC?

    <p>It suggests that Ofatumumab is more effective in CDC than Rituximab</p> Signup and view all the answers

    What is the relevance of the Teeling et al. (2004) study in the context of Ofatumumab?

    <p>It provided evidence for the effectiveness of Ofatumumab in killing tumor cells</p> Signup and view all the answers

    What is the primary advantage of in vitro antibody discovery over in vivo methods?

    <p>Higher throughput and efficiency</p> Signup and view all the answers

    What is the primary mechanism of antibody engineering?

    <p>Somatic hypermutation and class-switch recombination</p> Signup and view all the answers

    What is the focus of next-generation immuno-oncology?

    <p>Activating gdT cells and endogenous immune responses</p> Signup and view all the answers

    What is the primary challenge mentioned in the text for therapeutic antibodies?

    <p>Addressing 'high-hanging fruit' targets</p> Signup and view all the answers

    What is the technology used by FairJourney Biologics for antibody discovery?

    <p>Mammalian display</p> Signup and view all the answers

    What is the primary goal of antibody engineering in the context of cancer therapy?

    <p>Targeting tumor-specific antigens and activating immune responses</p> Signup and view all the answers

    What is the primary benefit of utilizing mammalian display technology for antibody lead discovery?

    <p>Selection of antibody variants with optimal biophysical properties and reduced immunogenicity</p> Signup and view all the answers

    What is the primary application of BTN3A antibodies in the context of cancer treatment?

    <p>Activation of gd T cells for immunotherapy</p> Signup and view all the answers

    What is the primary characteristic of CGRP antibodies that makes them effective in treating migraine?

    <p>Their ability to inhibit the release of CGRP from trigeminal nerves</p> Signup and view all the answers

    What is the primary advantage of using mammalian display technology over phage display for antibody lead discovery?

    <p>Mammalian display technology allows for the selection of antibodies with optimal biophysical properties and reduced immunogenicity</p> Signup and view all the answers

    What is the primary mechanism of action of Ofatumumab in killing tumor cells?

    <p>Induction of apoptosis in tumor cells through antibody-dependent cellular cytotoxicity</p> Signup and view all the answers

    What is the primary challenge mentioned in the text for therapeutic antibodies?

    <p>Reducing immunogenicity of antibodies</p> Signup and view all the answers

    Which technology is used to engineer the immune system?

    <p>Mammalian Display technology</p> Signup and view all the answers

    What is the primary mechanism of action of therapeutic antibodies as drugs in humans?

    <p>Inducing antibody-dependent cellular cytotoxicity</p> Signup and view all the answers

    What is the goal of optimizing human therapeutic antibodies?

    <p>To improve their specificity</p> Signup and view all the answers

    Which of the following is a future development in therapeutic antibodies?

    <p>Bispecific antibodies</p> Signup and view all the answers

    What is the name of the organization that provides data on approved antibody therapeutics?

    <p>Antibody Society</p> Signup and view all the answers

    What is the primary focus of the next generation of immuno-oncology?

    <p>Engineered gd T cells</p> Signup and view all the answers

    What is the primary advantage of therapeutic antibodies compared to other drugs?

    <p>Higher success rate in clinical trials</p> Signup and view all the answers

    What is the main limitation of therapeutic antibodies in terms of their target range?

    <p>They can only target cell surface or extracellular targets</p> Signup and view all the answers

    What is the primary reason for the limited penetration of therapeutic antibodies into the central nervous system?

    <p>Their large size limits their ability to cross the blood-brain barrier</p> Signup and view all the answers

    What is the primary factor that contributes to the high cost of therapeutic antibodies?

    <p>High production costs and large doses</p> Signup and view all the answers

    What is the primary benefit of therapeutic antibodies compared to other drugs in terms of their tolerance by patients?

    <p>They are mostly well tolerated by patients</p> Signup and view all the answers

    What is the significance of the 100 approved therapeutic antibody milestone reached in 2021?

    <p>It represents a significant achievement in the development of therapeutic antibodies</p> Signup and view all the answers

    What is the primary advantage of displaying antibody genes on the surface of bacteriophages?

    <p>Facilitated screening of antibodies with high affinities</p> Signup and view all the answers

    What is the characteristic of the antibody library constructed by Rene Hoet's group?

    <p>Features a combination of human-derived and synthetic antibody genes</p> Signup and view all the answers

    What is the primary goal of the phage selection process in antibody discovery?

    <p>To enrich for antibodies with high affinity for a target antigen</p> Signup and view all the answers

    What is the significance of the 3-23 framework in the context of antibody engineering?

    <p>It provides a scaffold for the design of synthetic antibody genes</p> Signup and view all the answers

    What is the outcome of the screening process in the FXIa antibody discovery example?

    <p>Selection of 198 unique clones with binding activity</p> Signup and view all the answers

    What is the characteristic of the antibody library generated by Dyax (now part of Shire/Takeda)?

    <p>It has a size of over 10^10 Fab fragments</p> Signup and view all the answers

    What is the primary mechanism underlying the pathophysiology of migraine?

    <p>Elevated plasma concentrations of calcitonin gene-related peptide (CGRP)</p> Signup and view all the answers

    Which of the following is NOT a brand name of a CGRP-targeting antibody for migraine treatment?

    <p>Rituximab</p> Signup and view all the answers

    What is the primary goal of 'Engineering the Immune System' in the context of therapeutic antibodies?

    <p>To optimize the discovery and optimization of monoclonal antibodies</p> Signup and view all the answers

    What is the target of the antibodies developed for migraine treatment?

    <p>CGRP receptor</p> Signup and view all the answers

    Which of the following is a characteristic of CGRP-targeting antibodies for migraine treatment?

    <p>They show prophylactic treatment of migraine</p> Signup and view all the answers

    What is the focus of the 'Pursuit of the high-hanging fruit' in the context of therapeutic antibodies?

    <p>Identifying new targets and improving the efficacy of antibodies</p> Signup and view all the answers

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