Report from the visiting committee

Section des Unités de recherche

Report from the visiting committee

Research unit : Cancer Immunotherapy

University Paris 5

Section des Unités de recherche

Report from the visiting committee

Research unit :

Cancer Immunotherapy

University Paris 5

Report from the visiting committee

The research unit :

Name of the research unit : Cancer Immunotherapy

Requested label : UMR_S

N° in case of renewal :

Head of the research unit : Mr Eric TARTOUR

University or school :

University Paris 5

Other institutions and research organization:

INSERM

Date(s) of the visit :

March 26th ₂₀₀₈

Members of the visiting committee

Chairman of the commitee :

Mr Thomas BROCKER

Other committee members :

Mr Muriel MASER

Mr Georges HERBEIN Mr Alberto EPSTEIN

CNU, CoNRS, CSS INSERM, représentant INRA, INRIA, IRD…..)

representatives :

Mrs Isabelle ANDRE-SCHMUTZ

No CNU representative was available at the date of the visit

Observers

AERES scientific representative:

Mrs. Ana CUMANO

University or school representative:

Mr Jean-Pierre MIALOT, Maisons-Alfort Veterinary School Mrs Marie-Claude LABASTIE, Paris Descartes University

Research organization representative (s) :

Mrs Christine TUFFEREAU, INSERM

Report from the visiting committee

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Short presentation of the research unit

Number of researchers or researchers with teaching duties : 6 Number of PhD students : 3

Number of post doctoral fellows : 3 Number of technicians or engineers : 1

Numbers of HDR 4, 2 of them who are PhD advisors

Number of students who have obtained their PhD during the last 4 years : 5 Number of publishing lab members : 6 out of 6

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Preparation and execution of the visit

The visit took place in the Veterinary School of Maisons-Alfort. In the morning the team leader introduced the Unit. JP Mialot talked in the name of the hosting institution. The team leader presented the project on pre-clinical development of the use of the b subunit of Shiga toxin as carrier for cancer vaccines. The scientific presentations included :

1. Preclinical program of vaccine in monkeys ;

2. Anti-leukemic vaccines in human: preclinical development of two different approaches in murine models ;

3. Analysis of the tumor micro-environment in head and neck cancer: Rationale for the development of immunotherapy

4. Anti-angiogenic and immunotherapy. The committee visited the laboratories and met with the senior scientists, students and post-doctoral fellows.

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Overall appreciation of the activity of the research unit, of its

links with local, national and international partners

The overall assessment of the Unit was good. The committee was impressed with the amount of work done in a short period of time and under particularly difficult conditions. Most work has to be performed between the Hospital and the laboratories in Maisons-Alfort. The lack of state of the art technical capabilities and large equipment at Maisons-Alfort was emphasized. One main topic of the group is immunomonitoring of anti-tumor T cell responses. However, in addition to analysis by ELISPOT, analysis by flow cytometry would be state-of-the-art and should eventually replace ELISPOT completely. The commission was especially astonished about the lacking/insufficient flow cytometry equipment, which should be central to the proposed projects. As the researchers and students have to travel with samples to other nearby hospitals and research institutes for analysis, these conditions appeared suboptimal to the commission.

The three projects on the use of beta subunit of Shiga toxin for cancer vaccines, anti-leukemic vaccines in humans and the analysis of the tumor microenvironment in head and neck cancer were considered coherent, while the last talk on the anti-angiogenic and immunotherapy was not consistent and without solid proof of concept. This latter approach lacks in many aspects a basic concept and is not properly focused. The work in non-human primates, which is very expensive and time consuming, should be revised. The group should establish external collaborations for this project. The type of experiments proposed, will (i) not result in sufficient information, (ii) not justify the costs and (iii) not justify the usage of primates. More sophisticated experiments should be attempted.

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Specific appreciation team by team and/or project by

project

• Of the quality of the management :

The quality of the management is good and students and post-doctoral fellows have an appropriate environment.

• Of human resources :

Compatible with the projects although the recruitment of a full time basic scientist, immunologist or cell biologist is recommended. This would strengthen the basic aspects of the projects and could ameliorate the day-to-day assistance/training for PhD-students at Maisons-Alfort.

• Of the communication strategy :

The communication strategies appears appropriate.

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Recommendations and advice

• Strengths :

The committee was impressed by the quality and amount of work done in a short period of time and under difficult conditions. The project of development of tumor vaccines using the Shiga toxin was considered interesting although a stronger focus on basic dendritic cell biology and mechanisms of shiga toxin/dendritic cell interactions would be beneficial. The project on anti-leukemic vaccines was also considered very interesting and should be continued, although the committee noticed that cancer stem cells, were not considered as potential targets for the vaccines.

• Weaknesses :

- technical/equipment : The general technical tools used are not up-to-date and the access to high end flow

cytometry should be ensured. The acquisition of a 2nd _{hand flow cytometer, as proposed, will not meet the required}

standards. The technical strategies should be more ambitious otherwise the proposed work may remain on a purely descriptive and less competitive status.

- planned projects : The work with primates raised doubts (necessary? feasible?). It was discussed that the

amount of work proposed and the costs do not justify the information that can be obtained. Collaboration with other groups working in the primate model would be beneficial. The work on anti-angiogenesis and immunotherapy was considered weak by the lack of proof of concept and less well related to the other subjects being developed.

• Recommendations :

The work should be focused on the strong projects. A more basic approach would improve the mechanistic insights and the recruitment of a full time post-doctoral fellow (immunologist or cell biologist) dedicated to the study of basic mechanisms of dendritic cells is recommended.