Lecture 6

Question 1

Recombinant IL-2 half-life

Answer 1

~3 mins

Question 2

What is Aldesleukin?

Answer 2

Recombinant IL-2

Question 3

Alpha subunit of IL-2 receptor

Answer 3

CD25

Question 4

Low doses of IL-2 activates __

Answer 4

Tregs

Question 5

High doses of IL-2 activates __

Answer 5

Effector T cells and Tregs (which is counterproductive)

Question 6

IL-2 paradox

Answer 6

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

Question 7

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

Answer 7

GVHD

Question 8

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

Answer 8

By using an anti-CD25 mAb like Basiliximab

Question 9

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

Answer 9

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

Question 10

IL-2 agonists

Answer 10

• 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)

Question 11

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

Answer 11

IFNα2

Question 12

IFNα indications

Answer 12

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

Question 13

Side effects of IFNα

Answer 13

Flu-like symptoms, depression, nausea, vomiting

Question 14

IFNα resistance

Answer 14

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

Question 15

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

Answer 15

CD28 and the CD3 co-receptor complex

Question 16

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

Answer 16

Tisagenlecleucel-T (Kymriah)

Question 17

CAR-T cell therapy for lymphoma

Answer 17

Axicabtagene ciloleucel (Yescarta)

Question 18

CAR-T cell therapy for diffuse large B cell lymphoma

Answer 18

Lisocabtagene maraleucel

Question 19

Risks associated with CAR-T cell therapy

Answer 19

• CRS
• Neurotoxicity

Question 20

3rd generation CAR incorporates…

Answer 20

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

Question 21

Examples of mAbs in oncology

Answer 21

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