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Antibody Engineering and Immune System

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

10^9 CFU

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

It generates high avidity C1q binding and efficient C3b deposition

What is the purpose of the Mammalian Display Platform?

To select antibodies for developability

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

It binds to a novel small loop epitope of CD20

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

FairJourney Biologics

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

Chronic lymphocytic leukemia

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

Anti-BTN3A Ab

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

To semi-synthetically design diverse repertoires

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

Arzerra

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

It is relatively insensitive to complement regulatory factors

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

Parthiban et al. (2019), Mabs: 11(5): 884-898

What is the format of Ofatumumab?

Humanized IgG1

What is the challenge mentioned in the given text?

Large library with 1 gene/cell

What is the benefit of using Mammalian Display?

Selection of clones with optimal biophysical properties

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

Multiple developability “red flags”

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

High immunogenicity

What is the goal of using Mammalian Display for Bococizumab?

To fix its developability properties

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

Dose escalation to Cohort 3

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

An increase in tumor infiltrating gd T cells, CD3, CD4 and CD8 T cells

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

To bridge the gap between new targets and new biologics drugs for patients

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

An increase in gd T cells and CD3+ T cells

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

Had a good safety profile with no DLTs or related SAEs

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

Specifically activated gd T cells after each dose

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

Achieving antibody diversity to the target

What is the purpose of glycosylation in human IgG?

Increasing therapeutic efficacy

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

Only CDRs are murine

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

In vitro technology uses mammalian display

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

CDR loops

What is the result of somatic mutations in antibody engineering?

Enhanced antibody diversity

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

Discussing the discovery and optimization of therapeutic antibodies

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

Phage display

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

Engineering the Immune System

Which immune cells are specifically targeted by BTN3A?

gd T-cells under stress

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

Activating gdT cells with anti-BTN3A antibodies

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

Over-expressed in solid tumors and down-regulated in blood cancers

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

FairJourney Biologics

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

Stimulation of stress-induced phosphoantigen production

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

CGRP

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

Team effort in building effective antibody products

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

Mammalian Display Technology

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

March 12, 2024

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

Immune-oncology

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

Genmab

What is the expression pattern of BTN3A in pancreatic tissues?

Differentially expressed in normal and pancreatic ductal adenocarcinoma

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

FXIa Ab development using phage display

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

To identify the most effective mAb for cancer therapy

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

The high hanging fruit

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

Complement-Dependent Cytotoxicity (CDC)

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

It binds to a novel small loop epitope

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

Humanized IgG1

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

Chronic Lymphocytic Leukemia (CLL)

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

It binds to a novel small loop epitope

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

It is more effective at low CD20 expression

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

Increase of gd T cells and CD3+ T cells infiltration

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

To bridge the gap between new targets and new biologics

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

It has a good safety profile

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

Dose escalation approval

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

Specific activation of gd T cells

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

Increase in tumor-infiltrating gd T cells, CD3, CD4, and CD8 T cells

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

To introduce the concept of antibody lead discovery and optimization

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

Rituximab (Roche, hybridoma technology)

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

Engineering the Immune System

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

Lecturer in Biopharmaceutics

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

FairJourney Biologics

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

CGRP (Migraine) antibodies

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

Combinatorial diversity of V, D, and J segments

What is the purpose of glycosylation in human IgG?

Improved therapeutic efficacy

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

Absence of murine CDRs

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

To generate antibodies with high diversity

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

CDR loops

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

Improved antibody diversity

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

Inducing phosphoantigen production under stress

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

To study the expression profile of BTN3A in pancreatic tissues

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

Activation of gd T cells under stress

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

Differential expression in solid tumors and blood cancers

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

Inducing gd T cell activation in response to phosphoantigens

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

Activating gd T cells in solid tumors

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

By ADCC and CDC

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

More efficient complement-dependent cytotoxicity

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

It is the target antigen for Ofatumumab

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

It implies that Ofatumumab can be used to target a broader range of tumor cells

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

It suggests that Ofatumumab is more effective in CDC than Rituximab

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

It provided evidence for the effectiveness of Ofatumumab in killing tumor cells

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

Higher throughput and efficiency

What is the primary mechanism of antibody engineering?

Somatic hypermutation and class-switch recombination

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

Activating gdT cells and endogenous immune responses

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

Addressing 'high-hanging fruit' targets

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

Mammalian display

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

Targeting tumor-specific antigens and activating immune responses

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

Selection of antibody variants with optimal biophysical properties and reduced immunogenicity

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

Activation of gd T cells for immunotherapy

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

Their ability to inhibit the release of CGRP from trigeminal nerves

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

Mammalian display technology allows for the selection of antibodies with optimal biophysical properties and reduced immunogenicity

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

Induction of apoptosis in tumor cells through antibody-dependent cellular cytotoxicity

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

Reducing immunogenicity of antibodies

Which technology is used to engineer the immune system?

Mammalian Display technology

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

Inducing antibody-dependent cellular cytotoxicity

What is the goal of optimizing human therapeutic antibodies?

To improve their specificity

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

Bispecific antibodies

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

Antibody Society

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

Engineered gd T cells

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

Higher success rate in clinical trials

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

They can only target cell surface or extracellular targets

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

Their large size limits their ability to cross the blood-brain barrier

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

High production costs and large doses

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

They are mostly well tolerated by patients

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

It represents a significant achievement in the development of therapeutic antibodies

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

Facilitated screening of antibodies with high affinities

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

Features a combination of human-derived and synthetic antibody genes

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

To enrich for antibodies with high affinity for a target antigen

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

It provides a scaffold for the design of synthetic antibody genes

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

Selection of 198 unique clones with binding activity

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

It has a size of over 10^10 Fab fragments

What is the primary mechanism underlying the pathophysiology of migraine?

Elevated plasma concentrations of calcitonin gene-related peptide (CGRP)

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

Rituximab

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

To optimize the discovery and optimization of monoclonal antibodies

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

CGRP receptor

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

They show prophylactic treatment of migraine

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

Identifying new targets and improving the efficacy of antibodies

Test your knowledge on antibody engineering, including combinational diversity, VDJ recombination, somatic mutations, and antibody format. Explore the specificity and affinity of human IgG1 and the importance of glycosylation in therapeutic applications.

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