Update on retroviral vector-mediated tumorigenesis

in gene transfer clinical trials

 

ERRATUM (modifications shown in bold, italic)

Appendix 4.

 

Table 1.  Comparison of X-SCID Retroviral Vector-Mediated Gene Transfer

 

Characteristic

Fischer [1]

Thrasher [2]

Weinberg*

Malech*

Cell Source

Bone Marrow

Bone Marrow

Bone Marrow

G-CSF mobilized CD34+ PBSC

CD34+ Selection

Miltenyi Biotec

CliniMACS

Isolex 300 I

Isolex 300I

Media

X-Vivo-10

X-Vivo-10

X-vivo-15

X-Vivo 10

Serum/Other

4% FCS

1% HSA

None

1% HSA

Cytokines (Source):

1.     Flt-3 ligand

 

2.     IL-3

 

3.     TPO

 

4.     MGDF

 

5.     SCF

 

6.     IL-6

 

 

300 ng/ml (Immunex)

60 ng/ml  (Novartis)

  -----------

 

100 ng/ml (Amgen)

300 ng/ml

(Amgen)

    ------------

 

300 ng/ml (R&D)

20 ng/ml  (R&D)

100 ng/ml

(R&D)

  ------------

 

  300 ng/ml

(R&D)

    ------------

 

 

 

300 ng/ml

(Immunex)

 ------------

 

 50 ng/ml

(R&D)

  -----------

 

50 ng/ml

(R&D)

  ------------

 

 

50 ng/ml

(R&D)

5 ng/ml

(R&D)

50 ng/ml

(R&D)

  --------------

 

50 ng/ml

(R&D)

25 ng/ml

(R&D)

Hrs Prestim.

24

40

40

18

Transduction

1.     Fibronectin

2.     Exposures

3.     Time

 

Yes

Three

72 hours

 

Yes

Three

56 hours

 

Yes

Three

72 hours

 

Yes

Four

78 hours

Vector Backbone

(LTR)

MFG

(MoMLV LTR)

MFG

(MoMLV LTR)

MND

(MPSV LTR)

MFG

(MoMLV LTR)

Vector Envelope (Packaging Line)

A-MuLV

(Psi-CRIP)

GaLV

(PG-13)

GaLV

(PG-13)

GaLV

(PG13)

1.          Hacein-Bey-Abina, S., et al., Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. New England Journal of Medicine, 2002. 346(16): p. 1185-1193.

2.          Gaspar, H.B., et al., Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Lancet, 2004. 364(9452): p. 2181-7.

* Details provided with kind permission from Drs. Weinberg and Podsakoff of The Saban Research Institute of Childrens Hospital Los Angeles, and Dr. Malech of NIH/NIAID.

Table 4.  Clinical Summary of ADA-SCID Trials

 

Investigator

Previous BMT/

Conditioning

Previous infectious or

other complications

Max Dose transplantedADA+ cells/kg

Longest time from treatment

Bordignon[3]

1 of 2 subjects

Busulfan conditioning

Yes

2.15 x 106

Approx 3.5 years

Kohn*

No Previous BMT

No conditioning

No

6.67 x 106

3.5 years

3.       Aiuti, A., et al., Gene therapy for adenosine deaminase deficiency. Curr Opin Allergy Clin Immunol, 2003. 3(6): p. 461-6.

 

*Details provided with kind permission from Drs. Kohn and Podsakoff of The Saban Research Institute of Children’s Hospital Los Angeles.  Conditions reflect methods used since 2001, not previously.