Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa

Table 1 Cohort characteristics at baseline and after treatment at last follow-up

Characteristic	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Subject 7
At baseline
Age at baseline (years)	23	19	32	18	32	32	45
Sex	M	M	M	M	F	M	F
Grafting year	2013	2014	2014	2015	2016	2016	2017
COL7A1 mutation 1, location	c.90delC, exon 2	c.90delC, exon 2	c.6527dupC, exon 80	c.8053 C > T, exon 109	c.4172dupC, exon 36	8440 C > T, exon 114	c.6176A > G, exon 73
COL7A1 mutation 2, location	c.5048_5051 dup4 (GAAA), exon 54	c.5048_5051 dup4 (GAAA), exon 54	c.7485 + 5 G > A, intron 98	c.7929 + (11_26) del16, intron 106	c.4182_4188dup7, exon 36	8440 C > T, exon 114	c.6501G > A, exon 79
NC1 expression by Western blot	NC1 +	NC1 +	NC1 +	NC1 +	NC1 +	NC1 +	NC1 +
Type VII collagen expression by IF^[a]	Undetectable NC1 and NC2	Undetectable NC1 and NC2	Trace NC1, Undetectable NC2	Undetectable NC1 and NC2	Undetectable NC1 and NC2	Undetectable NC1 and NC2	NC1 + , Undetectable NC2
Electron microscopy of skin biopsy	No mature AFs, sub-LD split	No mature AFs, sub-LD split	No mature AFs, sub-LD split	No mature AFs, sub-LD split	Rudimentary AFs, low LH24	Poorly formed AFs	Rudimentary AFs, low LH24
Circulating C7 antibodies^[b][c]	Negative	Negative	Negative	Positive	Negative	Negative	Negative
Prior history of SCC	No	No	No	No	Yes	No	No
After treatment at last follow-up
Age at last follow-up (years)	31	26	39	23	36	37	50
Follow-up period (years)	8	7	7	5	4	5	5
Presence of RCR in blood^[d]	No	No	No	No	No	No	No
Development of SCC at any location^[e]	No	No	No	No	Yes	Yes	No
Development of SCC at graft site	No	No	No	No	No	No	No
Vital status	Alive	Alive	Alive	Deceased	Deceased	Alive	Alive

[a] IF = immunofluorescence. All subjects were NC1 + when assayed by Western blot as required by inclusion criteria. NC1 status was assessed by IF anti-C7 LH 7.2 antibody, and NC2 status was assessed by IF with anti-C7 LH24 antibody
[b] Assayed by indirect IF using patient serum placed on monkey esophagus to detect C7 antibodies localized to dermal–epidermal junction
[c] All subjects had negative initial IIF studies for circulating C7 antibodies. In subject 4, circulating C7 antibodies were later observed in pre-treatment serum using Western blot, a more sensitive test, which was performed following evidence of immune response after treatment
[d] RCR = replication-competent retrovirus
[e] SCC = squamous cell carcinoma. SCCs were evaluated using polymerase chain reaction (PCR), and no evidence of viral vector was found in SCC samples

ISSN: 1750-1172