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BC4022 AM > Lecture 6 > Flashcards

Lecture 6 Flashcards

1
Q

Recombinant IL-2 half-life

A

~3 mins

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2
Q

What is Aldesleukin?

A

Recombinant IL-2

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3
Q

Alpha subunit of IL-2 receptor

A

CD25

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4
Q

Low doses of IL-2 activates __

A

Tregs

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5
Q

High doses of IL-2 activates __

A

Effector T cells and Tregs (which is counterproductive)

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6
Q

IL-2 paradox

A

IL-2 is a T cell growth factor, but Tregs scavenge IL-2 from the environment and have a lower threshold of response to IL-2 compared to Teff cells

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7
Q

Administration of low dose IL-2 has recently shown to be effective in __

A

GVHD

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8
Q

How can you block IL-2 from binding to its receptor?

A

By using an anti-CD25 mAb like Basiliximab

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9
Q

Indications for IL-2 blockade (i.e. Basiliximab)

A
  • Transplantation (prevention of renal allograft rejection)
  • T cell malignancies
  • Radiolabelled or toxin fusion enhances this anti-cancer effect
  • Autoimmunity: effective for MS
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10
Q

IL-2 agonists

A
  • Nektar (Bempegaldesleukin): IL-2 agonist that preferentially binds to β chain of IL-2R (CD122) on TILs to induce expansion of immune cells
  • Alkermes: fusion protein of IL-2/CD25 to induce clonal expansion of TILs (selectively targets intermediate affinity IL-2 receptors)
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11
Q

What was the first immunotherapeutic approved by the FDA for cancer?

A

IFNα2

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12
Q

IFNα indications

A

Hairy cell leukaemia, chronic myeloid leukaemia (CML), KSV, follicular lymphoma

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13
Q

Side effects of IFNα

A

Flu-like symptoms, depression, nausea, vomiting

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14
Q

IFNα resistance

A
  • Downregulation of IFNαR1
  • Upregulation of SOCS proteins
  • Modulation of Jak-STAT signalling
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15
Q

The cytoplasmic portion of the CAR contains elements from __ that replaces the need for co-stimulation of the CAR-T cell by CD80/CD86

A

CD28 and the CD3 co-receptor complex

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16
Q

FDA-approved CAR-T cell therapy for paediatric patients & young adults (up to age 25) with B-ALL

A

Tisagenlecleucel-T (Kymriah)

17
Q

CAR-T cell therapy for lymphoma

A

Axicabtagene ciloleucel (Yescarta)

18
Q

CAR-T cell therapy for diffuse large B cell lymphoma

A

Lisocabtagene maraleucel

19
Q

Risks associated with CAR-T cell therapy

A
  • CRS
  • Neurotoxicity
20
Q

3rd generation CAR incorporates…

A

two distinct co-stimulatory domains i.e. both CD28 & 4-1BB

21
Q

Examples of mAbs in oncology

A
  • Tumour-specific IgG
  • Checkpoint blockade
  • CAR-T cells
  • Bi-specific antibody therapy
  • Antibody drug conjugate therapy
  • Radioimmunotherapy

BC4022 AM (8 decks)

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