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TREATMENT OF NON-HODGKIN S LYMPHOMA USING ALPHA-RADIOIMMUNOTHERAPY

Objective

The main objective of this project is the demonstration on a European and worldwide level of the required steps to prepare a new drug for the therapeutical treatment of cancer based on alpharadioimmunotherapy. The products, techniques and installations to be validated are situated in the frame of blood borne cancer treatment both when applying autologous bone marrow transplantation (ABMT) or haematopoietic stem cell rescue (HSCR) ex-corpore and when treating minimal residual disease (MRD) in-vivo.
Alpha-emitting nuclides and their daughter products will be used because of their favourable characteristics for the subject application (high linear energy transfer and therefore good cancer cell killing efficiency, short range and therefore minimal healthy cell killing). The short half-life of the alpha-emitting nuclide 213 Bi (45.6 minutes) also minimises the residual radioactivity both for the ex-corpore and the in-vivo treatment. The selection of B-cell malignancies for the demonstration of this innovative cancer therapy is based on the fact that blood and/or bone marrow borne cancers are the prime candidates to search for new purging techniques ex-corpore to reduce the residual cancer cell burden and the fact that they are ideally suited for alpha-immunotherapeutical treatment (e.g. for minimal residual disease) in-vivo using short lived radioisotopes.
Non-Hodgkin's Lymphoma (NHL) was selected based on the finding that most patients with advanced-stage follicular lymphoma cannot be cured with conventional cytotoxic therapy and that the presence of minimal residual disease in bone marrow is a negative prognostic factor. For NHL the CD22, CD19 and CD20 antigen selective antibodies are well documented and some were tested already in their coupling to iodine or yttrium isotopes. The increase of both the awareness and potential acceptance of this therapy are envisaged by implementing quality controlled production and purification, the in-vitro and in-vivo testing, the ex-corpore evaluation and phase 1 clinical trials of the alpha-radiopharmacon.
This project will validate the products, techniques and installations as described and offer an approved supplementary treatment. In a second step, the use in-vivo will be evaluated by implementing animal testing BALB/C mice will be used for general safety testing, biodistribution, toxicology and histopathology. Dose analysis of the radioimmunoconjugate administered to BALC/C mice will be made and extrapolated to prepare for clinical phase 1 testing on patients having undergone all other approved therapies without success. Patient treatment is planned in a medical equipped facility having the license to work with alpha-emitters. Because of the short half-life of the isotopes used, the patients could however quickly be transported to a normal hospital for further medical follow-up.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITY HEIDELBERG
Address
Hospitalstrasse 3
69115 Heidelberg
Germany

Participants (3)

Deutsches Krebsforschungszentrum
Germany
Address
Im Neuenheimer Feld 280
69120 Heidelberg
INSTITUTE FOR TRANSURANIUM ELEMENTS ; EUROPEAN COMMISSION
Germany
VIRGA-JESSE HOSPITAL
Belgium