Immunotherapy

Question 1

What is immunotherapy?

Answer 1

Targeting of disease by activating or suppressing the immune system?

Question 2

What are the different types of immunotherapy?

Answer 2

Vaccines
Immunomodulatory Drugs
Biologicals
Cell Therapies

Question 3

What diseases can we treat with immunotherapy?

Answer 3

Cancer
Chronic Infections
Autoimmune Diseases
Allergy
Transplant rejection

Question 4

What is a vaccine comprised of?

Answer 4

Antigen + Adjuvent (provides DAMP signal e.g. Alum - PRR Nalp3

Question 5

What are the two types of vaccine?

Answer 5

Prophylactic - given to prevent chronic disease/cancer

Therapeutic - given to people with the disease

Question 6

How do propylactic vaccines work?

Answer 6

Induce adaptive immune response and generate immunological memory:

Memory T cells - TCM (CD45RO - CCR7+ve), TEM (CD45RO - CCR7-ve)

Memory B cells (IgG/IgA - effector functions, somatic hypermutation (increased affinity), increased frequency)

Question 7

What are some examples of prophylactic vaccines against infectious diseases

Answer 7

Attenuated - MMR, Sabin Polio, Yellow Fever, BCG

Question 8

What is a vaccine used for cancer?

Answer 8

Ceravix - HPV - cervical cancer

Question 9

What are some of the new vaccines?

Answer 9

DNA vaccines - insert viral plasmid with Ag and adjacent DNA using gene gun - safer (no pathogen), can quickly change Ag genes when mutations occur, quick/easy (one step cloning) - HIV-1 - no current licensed

DC Vaccines - Ovarian Cancer, Wilms Tumour

Question 10

What are immunomodulatory drugs?

Answer 10

Small molecules which interferes with cell receptors, signalling pathways, enzymes etc.

Question 11

What are some examples of stimulatory immunomodulatory drugs?

Answer 11

Cancer/Infections - TLR ligands (LPS, CpG), Cytokines (IFN), chemokines, IDO inhibitors

Question 12

What are some examples of suppressive immunomodulatory drugs?

Answer 12

Tacrolimus - immune suppression for graft rejection - inhibits IL-2 - prevents T cell proliferation - more potent and effective version of cyclosporin (46 % vs 30%)

Question 13

How do IDO inhibitors work?

Answer 13

IDO (Idoleamine 1,2 Dioxygenase) catabolised metabolism of tryptophan in TME - results in increase of Treg and reduction of effector T cells

Inhibitors of this such as indoximod prevent this and so increase effector T cells against tumour cells

Question 14

What are biologicals?

Answer 14

Drug developed using a living system

Question 15

How do we produce mAbs?

Answer 15

Fusion (using PEG) of B cells with (Ig negative ) myeloma cells to provide a hybridoma

Question 16

How do we humanize mAbs?

Answer 16

CDR grafting - reduce HAMA response (type 3 hypersensitivity response)

Question 17

What are the three classes of mAbs for cancer therapy?

Answer 17

1) Naked mAbs (ADCC, immune checkpoint, receptor targeting)
2) Conjugated
3) Bispecific

Question 18

What are some examples of naked mAbs for cancer therapy?

Answer 18

1 - ADCC - adelizumab - bind CD52 and localise NK cells to induce apoptosis (ALL)

2 - Immune checkpoint - PD1/PDL1 - nivolumab - CTLA4/B7 - Ipilimumab

3 - Herceptin - HerC - receptor in breast cancer responsible for growth and development of cells - binding of Herceptin causes internalisation and degradation of receptor

Question 19

What is an example of a conjugated mAb for cancer therapy?

Answer 19

Zevalin - radiolabelled - CD20 - NHL

Question 20

What is an example of a bispecific mAb for cancer therapy?

Answer 20

Blinatumomab - BiTE - CD19 (malignant B cell) and CD3 (T cell)

Question 21

How does Car-T Therapy work?

Answer 21

Chimeric Antigen Receptor T cell therapy - involves removal of T cells (leukaphresis) and modifying T cells to make them more effective against tumour cells - NHL, ALL - severe side effects - Seizures, low BP, confusion