Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y Immunology > Seminar 10 - Immunotherapies (Ben) > Flashcards

Seminar 10 - Immunotherapies (Ben) Flashcards

1
Q

Explain how an unconjugated monoclonal antibody (mAb) could be used therapeutically.

A
  • mAb targeting a cell surface marker (e.g. CD19/CD20 on B cells) can bind it and activate several pathways for removal of the cell:
    • classical complement -> lysis
    • FcR-mediated phagocytosis
    • ADCC via NK cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the short term and long term issues which may arise when using mAb therapy?

A
  • short term: may produce IgE against the mAb -> anaphylactic rxn
  • long term: may produce IgG against mAb -> elimination of mAb via phagocytosis, etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are chimeric/humanized mAbs?

A
  • chimeric mAbs are human in origin except for the variable regions (usually murine)
  • CDR-grafted mAbs - contain human CDRs, only small parts of the variable region are murine
  • used to avoid immune reactons that often occur against completely murine/xenogenic mAbs which can cause anaphylaxis or inactivation of the mAb
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

In naming of mAb therapies…

what does U mean?

O?

Xi?

Zu?

A
  • U = human
  • O = murine
  • Xi = chimeric
  • Zu = humanized
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

In naming of mAb therapies…

what does “Li” mean?

Tu?

Ci?

Cept?

A
  • Li = immunomodulating
  • Tu = antitumoral
  • Ci = against CV disease
  • Cept = non-antibody based signal interception
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can antibody fragments be used in mAb therapy?

Advantages / disadvantages?

A
  • Fab (antigen binding fragments) can be used
  • advantages: specificity, small size, efficient penetration + lack of Fc decreases non-specific binding
  • disadvantage: short life span
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give examples of 2 mAb therapies against specific breast/gastric cancers + their mechanisms.

(not sure that we need to know the drug names specifically, but maybe the target is important)

A
  • Herceptin - “trastuzumab” humanized antibody against Her2/neu growth factor receptor on breast/gastric cancers; blocks receptor + induces anti-tumor ADCC
  • Kadcyla - trastuzumab linked to cytotoxic agent “mertansine”; kills tumor with cytotoxic ligand
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What mAb drug can treat chronic inflammatory disorders such as psoriasis + psoriatic arthritis by eliminating cytokines?

What is its target?

(again, don’t know how important specifc drug is, but mechanism may be more important)

A
  • Stelara - “ustekinumab” - a human mAb against P40 a common subunit of IL-12 + IL-23
  • by neutralizing these cytokines via binding their common subunit, the drug can decrease Th1/Th17/NK responses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What mAb therapy can be used in Crohn’s disease + MS?

What is its mechanism/target?

(aaand again, mechanism is probably more important than drug name)

A
  • Tysabri - “natalizumab” targets integrin alpha 4 (ITGA4), a molecule which induces T cell homing to the brain + GI tract
  • thereby reduces leukocyte infiltration and local inflammatory responses in Crohn’s/MS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What mAb therapy can be used to activate T-cell responses against cancers?

Mechanism + target?

A
  • Ramovab - “catumaxomab” bi-specific Ab against CD3 and EpCAM (epith. cell adhesion molecule)
  • links EpCAM+ tumor cell to CD3+ T cell -> induces anti-tumor CTL lysis
  • its Fc region also binds NK cells -> induces ADCC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What mAb drug eliminates mature lymphocytes as an immunosuppressive and anti-leukemic/lymphoma therapy?

Target / mechanism?

A
  • Lemtrada - “alemtuzumab” - against CD52 found on mature lymphocytes
  • labels cells for elimination via ADCC + complement lysis
  • treats leukemias/lymphomas; used for marrow/kidney transplant prep; treats MS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Based on the last 5 cards…

what are 5 general mechanisms by which mAb drugs can have therapeutic effects?

(i think these general mechanisms are more important than any of the specific drug names / molecular targets, as far as possible test questions go)

A
  1. Cancer growth factor receptor blockade
  2. Cytokine neutralization
  3. Homing inhibition
  4. Local T cell activation
  5. Lymphocyte elimination (immunosuppression)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe IVIG therapy.

(indications, mechanisms, etc.)

A
  • IV admin. of polyvalent IgG from collected from many human donors
  • Indications: immunodeficiencies; autoimmunity; some infections; chronic inflammatory disorders
  • mechanism: restores IgG responses; neutralizes auto-antibodies; ADCC; receptor interactions (blocking/modulation, etc.)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Give an example of how recombinant cytokines can be used therapeutically.

A
  • Proleukin - recombinant IL-12 induces “hyper-aggressive” cellular immunity against cancers
  • indications: metastatic melanoma + renal cell cancers
  • mechanisms: many mechanisms, mostly unknown; CTL/NK cell prolif.; tumor-associated macrophage activity; increased anti-tumor Th1 responses (IFN-y, TNF, IL-1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What drug consisting of a synthetic Th1 cytokine can be used as an anti-viral and anti-cancer immunotherapy?

For what diseases? Via what mechanisms?

A
  • PEG-interferon-alpha 2a/2b (“PegIntron”)
  • for Hep B/C, Kaposi’s sarcoma, leukemias
  • mechanisms: proteosome stimulation; incr. MHC expression; incr. CTL/NK activity; decr. protein synth/RNA stability in somatic cells; tumor/viral apoptosis; decr. tumor vascularization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What bacterial vaccine can also be used as an immunotherapy against a certain form of cancer?

A
  • BCG vaccine - Bacillus Calmette-Guerin attenuated M. bovis
  • indication: superficial bladder cancer
  • mechanism: PRR activation; granuloma formation; cytokine release; NK/CTL/macrophage stimulation
17
Q

How can intentional induction of GVH disease be used therapeutically?

A
  • in hematologic malignancies treated with bone marrow transplant
  • after normal hematopoietic stem cell transplant, extra allogenic T cells from the donor can be given
  • this increases the GVH response + can help clear residual/relapsing leukemia cells
18
Q

How does IVIG treatment work against autoimmune conditions?

A

Via two receptors

  • FcyRIIb - Fc portion of injected IgGs binds this inhibitory R on B cells and inactivates them
  • FcRn - neonatal FcR also on adult endothelial cells; binds Ig + endocytoses, may protect autoantibodies this way; occupying this R with extra IgG -> breakdown of non-endocytosed auto-Abs
19
Q

What medication uses a modified virus to infect/fight cancer cells?

How?

A
  • Worst name ever: Imlygic (Talimogene laherparepvec)
  • Uses engineered HSV which only infects cancer cells (b/c it lacks a certain protein needed to infect normal ones)
  • virus mediates oncolysis: infected cancer cells express viral proteins via MHC-I -> increased CD8+ lysis; virus secretes GM-CSF -> activates APCs
20
Q

What molecule plays a central role in rheumatoid arthritis and what 3 general mechanisms does it contribute to in the disease process?

A

TNF-alpha

  • ​incr. production of pro-inflammatory mediators (NO, PGs, etc.)
  • incr. proteases -> matrix degradation
  • incr. chemokine/adhesion molecule expression -> leukocyte recruitment
21
Q

What two types of TNF-alpha targeting medications are used for RA?

A
  1. Anti-TNF mAbs - infliximab, etc.; bind + inactivate TNF
  2. Soluble TNF receptors - etanercept; a hybrid of soluble TNFR and IgG Fc portion (to extend its half-life in blood)
22
Q

What are some (6) potential complications of TNF blockade therapies?

A
  1. Hypersensitivity Rxns
  2. Tumor development
  3. Hepatic problems
  4. SLE
  5. CHF
  6. Infectious Disease
23
Q

What infections are commonly increased by TNF blockade therapies?

A
  • Most common: UR infections
  • Others: ​tuberculosis; erysipelas; joint/bone infection; hepatitis
24
Q

How can antibody levels be decreased as therapy against RA?

(drug, mechanism, other indications etc.)

A
  • Rituximab - anti B cell antibody
  • binds CD20 on differentiating B cells (not plasma cells!)
  • leads to B cell depletion via ADCC, complement, apoptosis -> decr. Ab levels
  • also used in non-Hodgkin lymphoma
  • (being tested for SLE, Hep C, Sjogrens, Wegener’s granulomatosis)
25
Q

How is T cell activity targeted as therapy for RA?

(drug name, mechanism, etc.)

A
  • Abatacept - soluble combination of CTLA-4 and IgG Fc
  • CTLA-4 is an inhibitory receptor on T cells which binds B7, preventing B7->CD28 T cell co-stimulation
  • soluble CTLA-4 as a drug can bind B7 and prevent its stimulation of T cells; conjugation to IgG Fc increases its serum half life
26
Q

How can monoclonal Abs be used to avoid “aspecific” effects of treatments on cells other than the intended target cells?

A
  • toxins, drugs + radioactive isotopes can be conjugated to mAbs specifc for molecules of the target cell
  • this allows “targeted” therapies which avoid having negative/toxic effects on other cells throughout the body
27
Q

What are bispecific antibodies and how can they be used therapeutically?

A
  • Abs with binding sites for two different antigens
  • can be used to connect two different cell types, such as cytotoxic T cells and cancer cells, to induce their interaction

Y Immunology (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions