Simple explanation
Blood cancers start in the cells of the bone marrow and blood. They are the cancers where engineered immune cell therapy has worked best, because the cancer cells circulate where the treatment can reach them and carry surface markers the engineered cells can be aimed at. This is also where a gene-edited treatment first saved a life: in 2015, an infant with leukaemia who had run out of options received donor immune cells edited with TALENs.
Go deeper
Haematological malignancies are the leading indication for engineered cell therapy. Editing enables allogeneic products through TRAC knockout (preventing graft-versus-host disease) and B2M or CIITA knockout (delaying host rejection). CD19 and CD7 are common targets; CD7-directed products additionally require editing to prevent fratricide between the engineered cells themselves.
The Layla Richards case
In 2015 clinicians at Great Ormond Street Hospital treated an infant with relapsed acute lymphoblastic leukaemia using TALEN-edited donor T cells, under compassionate use, after conventional treatment failed. She went into remission. It was the first use of gene-edited cells in a patient and it happened years before CRISPR reached the clinic — a reminder that gene editing did not begin with CRISPR.
Sources
- Science Translational Medicine (Qasim et al.) · 2017
Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells ↗