Back

Notification report


General information

Notification Number
B/FR/05/03/04

Member State to which the notification was sent
France

Date of acknowledgement from the Member State Competent Authority
08/02/2005

Title of the Project
Pluriannuals field experimentations of genetically modified maize expressing monoclonal antibodies RM2 and RM3 for medical uses in cancerology.

Proposed period of release:
01/04/2005 to 31/10/2006

Name of the Institute(s) or Company(ies)
Meristem Therapeutics, ;


3. Is the same GMPt release planned elsewhere in the Community?
No

Has the same GMPt been notified elsewhere by the same notifier?
No

Genetically modified plant

Complete name of the recipient or parental plant(s)
Common NameFamily NameGenusSpeciesSubspeciesCultivar/breeding line
maizepoaceaezeazea maysmaystwo populations (one by antibody)

2. Description of the traits and characteristics which have been introduced or modified, including marker genes and previous modifications:
The genes introduced confer to the maize:
- Ability to produce a monoclonal antibody (one by event of transformation) in seeds
- Tolerance to glufosinate ammonium
There has been no previous genetic modification of the parental organism.


Genetic modification

3. Type of genetic modification:
Insertion;

In case of insertion of genetic material, give the source and intended function of each constituent fragment of the region to be inserted:
A binary plasmid which was introduced in a disarmed Agrobacterium strain has been used. The vector contains:
- a gene fusion between a signal peptide sequence isolated from tobacco pathogenesis related protein and a sequence that encodes a heavy chain of a human monoclonal antibody directed against one epitope issued from human cancerous cells. This gene fusion is under the control of the maize zein promoter (seed specific expression).
- a gene fusion between a signal peptide sequence isolated from tobacco pathogenesis related protein and a sequence that encodes a light chain of a human monoclonal antibody directed against one epitope issued from human cancerous cells. This gene fusion is under the control of a promoter derived from the wheat high-molecular-weight-glutenin promoter (seed specific expression).
- the bar coding sequence from Streptomyces hygroscopicus. This gene used as a selective marker confers tolerance to glufosinate ammonium (constitutive expression).

For each of the two antibodies produced (RM2 and RM3) one heavy chain and one light chain are expressed.


6. Brief description of the method used for the genetic modification:
The method used is the biologic transformation by Agrobacterium tumefaciens.

7. If the recipient or parental plant is a forest tree species, describe ways and extent of dissemination and specific factors affecting dissemination:
Not applicable

Experimental Release

1. Purpose of the release:
The goal of this release is to obtain grains producing these monoclonal antibodies in order to:
o develop the extraction /purification process at pilot scale,
o produce enough antibodies in order to start pre clinical and clinical trials,
o confirm biological activity of each of these antibodies obtained,
o continue the comparison between recombinant antibodies produced from animal cell culture and from plants,
o compare results obtained with plants from greenhouse and from field.


2. Geographical location of the site:
In 2005 the release is planned in the center of France (Puy de Dôme, Auvergne).

3. Size of the site (m2):
15 000 m2 on one site (including non transgenic border rows, and non transgenic maize used as pollinators).

4. Relevant data regarding previous releases carried out with the same GM-plant, if any, specifically related to the potential environmental and human health impacts from the release:
First field release.
Previous greenhouse productions have not shown any particular behaviour of those GMPts.


Environmental Impact and Risk Management

Summary of the potential environmental impact from the release of the GMPts:
- No selective advantage is expected by the expression of these monoclonal antibodies in seeds of GMPts
- Tolerance to the glufosinate ammonium, is a benefit only if the herbicide is used.
- There is no wild species sexually compatible with maize in Europe so potential interspecific crossings are not possible in these sites. The only potential crossing can be between GMPts and conventional maize. However this type of crossing is very improbable due to the fact that measures are taken for the control of non intentional release in the environment and pollen dissemination (Cf. paragraph E).
- The in vitro and in vivo experimental studies carried out have shown the specificity and the efficiency of these antibodies against certain human cancerous cells. The first assays of injection to mice have not revealed toxic effect.
- Except the specific cultivation management, the techniques of cultivation used are the same ones as those usually used for conventional maize production. So no supplemental effect is expected for environment.
- To our knowledge, no risks to human and animal health or the environment from the deliberate release of genetically modified maize expressing these monoclonal antibodies and tolerance to glufosinate ammonium herbicide have been reported.


Brief description of any measures taken for the management of risks:
- Transgenic maize will be detasseled and pollinated by non transgenic maize.
- Experimental plot will be isolated from any commercial maize field by at least 200 m.
- At least 4 border rows of non transgenic maize will be sown all around the experimental plot.
- Destruction by crushing of the residues of culture at the end of the harvest.
- Monitoring of possible volunteers during one year after harvest.
- No commercial corn culture will be established on this experimental field the following year.
- Maize will not be used for feed or food.

The regular follow-up of the trials makes it possible to identify in an early way any event or development which is not desirable. Thus the trials can be stopped quickly by the classic means of destruction (chemical treatment with a conventional total herbicide other than the glufosinate ammonium or mechanical treatment with crusher for example).


Summary of foreseen field trial studies focused to gain new data on environmental and human health impact from the release:
Not applicable

Final report
-

European Commission administrative information

Consent given by the Member State Competent Authority:
Yes
27/04/2005 00:00:00
Remarks: