PERSONALIZED THERAPY OF BLOOD CANCERS
o Patients can be categorized and group them together into patients who might benefit from standard
therapy and discrete, smaller groups of patients based on their individual genetic and protein
expression profiles and other aspects that might benefit from targeted therapy.
Blood cancers are genetically very simple and possess small numbers of genetic aberrations which
could readily be identified and targeted rather than the hundreds of abnormalities which can be present
in solid tumours.
We can readily sample the tumour tissue because often the cells are present in the circulating blood.
This characteristic of blood cancer allows us to map the evolution of subsequent genetic abnormalities
and their functional impact as cancer evolves.
Specific Pathways Targets in Personalized Medicine
o Blood cancer cells can express a characteristic of cell surface
markers. This often doesn’t differentiate them from healthy cells.
But it can allow us to target these cells with monoclonal antibodies
or with other technologies.
o Blood cancer cells have a raft of deranged cell signalling pathways
which often result from over activity of membrane bound tyrosine
kinase.
o Epigenetic abnormalities in blood cancer can also be detected.
, Monoclonal antibody therapy allows us to target
proteins with incredible specificity on the
surface or within cells.
Monoclonal antibodies can be used to directly
target tumour cells via proteins expressed on
their surface.
Monoclonal antibodies can be conjugated to a
drug that deliver a local payload of therapy.
Monoclonal antibodies can also block immune
checkpoint. It revolutionized immuno-oncology.
Double ended therapy targets protein on a
tumour cell but the other end of the molecule
targets the CD3 receptor on a T cell. Thus
engaging the adaptive immune system.
Another therapy method is the T cells which
having their specificity redirected by having an immunoglobulin-like molecule in deserted
virotransmembrane domain which can directly bind to protein on a tumour cell.
Rituximab
CD20 target drug.
Indications: non Hodgkin lymphoma (DLBCL,MCL), CLL , Non-cancer
(autoimmune conditions)
Lead to development of fully human mAb (Ofatumumab- CLL).
Side effects: infusional reactions, worse on 1st exposure.
Brentuximab
Conjugated antibody.
CD30 is the target which is an activation
marker on B cells’ anti cells and its over
expressed in some haematologic
malignancies.
Ways Blood Cancer Cells Evade mAb
* Major mechanism is down regulation of expression of cell surface targets.
* CD20- minor problem
* CD19 (target of CAR T and Bi-specific mAbs)- major problem. Underlies 50% of relapses. Linked to
selective expression of splice variants of CD19.
o Patients can be categorized and group them together into patients who might benefit from standard
therapy and discrete, smaller groups of patients based on their individual genetic and protein
expression profiles and other aspects that might benefit from targeted therapy.
Blood cancers are genetically very simple and possess small numbers of genetic aberrations which
could readily be identified and targeted rather than the hundreds of abnormalities which can be present
in solid tumours.
We can readily sample the tumour tissue because often the cells are present in the circulating blood.
This characteristic of blood cancer allows us to map the evolution of subsequent genetic abnormalities
and their functional impact as cancer evolves.
Specific Pathways Targets in Personalized Medicine
o Blood cancer cells can express a characteristic of cell surface
markers. This often doesn’t differentiate them from healthy cells.
But it can allow us to target these cells with monoclonal antibodies
or with other technologies.
o Blood cancer cells have a raft of deranged cell signalling pathways
which often result from over activity of membrane bound tyrosine
kinase.
o Epigenetic abnormalities in blood cancer can also be detected.
, Monoclonal antibody therapy allows us to target
proteins with incredible specificity on the
surface or within cells.
Monoclonal antibodies can be used to directly
target tumour cells via proteins expressed on
their surface.
Monoclonal antibodies can be conjugated to a
drug that deliver a local payload of therapy.
Monoclonal antibodies can also block immune
checkpoint. It revolutionized immuno-oncology.
Double ended therapy targets protein on a
tumour cell but the other end of the molecule
targets the CD3 receptor on a T cell. Thus
engaging the adaptive immune system.
Another therapy method is the T cells which
having their specificity redirected by having an immunoglobulin-like molecule in deserted
virotransmembrane domain which can directly bind to protein on a tumour cell.
Rituximab
CD20 target drug.
Indications: non Hodgkin lymphoma (DLBCL,MCL), CLL , Non-cancer
(autoimmune conditions)
Lead to development of fully human mAb (Ofatumumab- CLL).
Side effects: infusional reactions, worse on 1st exposure.
Brentuximab
Conjugated antibody.
CD30 is the target which is an activation
marker on B cells’ anti cells and its over
expressed in some haematologic
malignancies.
Ways Blood Cancer Cells Evade mAb
* Major mechanism is down regulation of expression of cell surface targets.
* CD20- minor problem
* CD19 (target of CAR T and Bi-specific mAbs)- major problem. Underlies 50% of relapses. Linked to
selective expression of splice variants of CD19.
