Immune Therapy Flashcards
There are many types of MAb therapies for cancer. Broadly speaking, what mechanisms kill cancer?
Blockage of receptor-mediated signaling required for tumour growth / survival.
Marking tumour cell for immune mediated destruction.
What cancer type is Rituximab used for?
Which group of patients show enhanced response?
Follicular Non-Hodgkin’s Lymphoma (esp. relapsed and refractory cases)
targets CD20
Patients with lymphoma and polymorphism encoding high-affinity FcR.
Chimeric Ab = Human IgG1 Fc fragment and remaining mouse Ab.
Why do certain patients become resistant to Rituximab?
Alterations in CD20 expression
Elevated apoptotic resistance
Loss of complement activity (as Rituximab kills cells via CMC).
Can can regulatory T cells be targeted?
Treg survival - Paclitaxel
Treg generation - Inhibit A2a receptors
Treg migration - target CCL22 or CXCR4
Treg expansion - tyrosine kinase inhibitors e.g. imatinib.
What are the targets of CAR T cell therapy for solid malignancies?
CD28 and CD36 in prostate cancer
HER-2 being trialled.
What haematological malignancy has shown great promise for CAR T cell treatment?
B-ALL - CD-19 specific - main issue is induction of immune responses which in severe cases can –> death.
CD-19 targeted therapies are less effective for other B-cell malignancies.
What is a CAR T cell?
single chain construct - extracellular Ig variable domain is fused to a TCR constant domain.
Combines An recognition properties of Ab with T cell lytic functions.
What is the rationale behind mAbs directed against CTLA4 and PD1?
they neutralize the co-inhibitory receptors. Blocking intrinsic immune checkpoints –> allows sustained T cell responses inc. cytolytic activity and cytokine production.
In autologous vaccine primed in vitro expanded T cell therapy how are tumour specific T cells selected for?
Isolate TILS and culture with IL-2
Therapeutic TILS reinfused into patient –> reinfiltrate tumour, inducing lysis and tumour regression.
How successful are anti-CD19 CAR T-cell therapies?
> 80% cure rates in clinical trials but also emergence of escape clones.
