Immunotherapy Flashcards
What is immunotherapy?
Targeting of disease by activating or suppressing the immune system?
What are the different types of immunotherapy?
Vaccines
Immunomodulatory Drugs
Biologicals
Cell Therapies
What diseases can we treat with immunotherapy?
Cancer Chronic Infections Autoimmune Diseases Allergy Transplant rejection
What is a vaccine comprised of?
Antigen + Adjuvent (provides DAMP signal e.g. Alum - PRR Nalp3
What are the two types of vaccine?
Prophylactic - given to prevent chronic disease/cancer
Therapeutic - given to people with the disease
How do propylactic vaccines work?
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)
What are some examples of prophylactic vaccines against infectious diseases
Attenuated - MMR, Sabin Polio, Yellow Fever, BCG
What is a vaccine used for cancer?
Ceravix - HPV - cervical cancer
What are some of the new vaccines?
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
What are immunomodulatory drugs?
Small molecules which interferes with cell receptors, signalling pathways, enzymes etc.
What are some examples of stimulatory immunomodulatory drugs?
Cancer/Infections - TLR ligands (LPS, CpG), Cytokines (IFN), chemokines, IDO inhibitors
What are some examples of suppressive immunomodulatory drugs?
Tacrolimus - immune suppression for graft rejection - inhibits IL-2 - prevents T cell proliferation - more potent and effective version of cyclosporin (46 % vs 30%)
How do IDO inhibitors work?
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
What are biologicals?
Drug developed using a living system
How do we produce mAbs?
Fusion (using PEG) of B cells with (Ig negative ) myeloma cells to provide a hybridoma
How do we humanize mAbs?
CDR grafting - reduce HAMA response (type 3 hypersensitivity response)
What are the three classes of mAbs for cancer therapy?
1) Naked mAbs (ADCC, immune checkpoint, receptor targeting)
2) Conjugated
3) Bispecific
What are some examples of naked mAbs for cancer therapy?
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
What is an example of a conjugated mAb for cancer therapy?
Zevalin - radiolabelled - CD20 - NHL
What is an example of a bispecific mAb for cancer therapy?
Blinatumomab - BiTE - CD19 (malignant B cell) and CD3 (T cell)
How does Car-T Therapy work?
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
