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Therapeutic targeting of colorectal and other carcinoembryonic antigen (CEA) positive cancers with a recombinant divalent antibody fragment (CIGB-M3) |
Therapeutic area |
Cancer |
Goal |
To develop novel therapeutic strategies via the specific targeting of colorectal and other CEA+ cancers with recombinant antibody fragments. |
Description |
The CIGB has developed over the last 15 years a technological platform related to the development of recombinant antibody fragments from mouse hybridoma material and human antibody libraries, and their expression/production in E. coli, Pichia pastoris, and transgenic plants.
As part of this work, the variable regions genes of a proprietary anti-CEA mouse monoclonal antibody (Mab) were cloned and expressed as a multivalent scFv recombinant antibody fragment of the diabody type (denominated CIGB-M3) in E. coli. The 99mTc-radiolabeled original mouse Mab is registered in Cuba for colorectal cancer monitoring, and has been the subject of successful international multicenter studies. The ca. 50 kDa CIGB-M3 diabody could be advantageous over the original Mab in the radio immunotherapeutic (RIT) scenario, due to better tumor penetration, faster clearance, and reduced immunogenicity, while preserving adequate tumor retention because of its divalent nature.
After radiolabeling with 125I and 131I CIGB-M3 showed excellent biodistribution in nude mice bearing human CEA+ tumors (Pérez et al. Biotechnol. Appl. Biochem. 43(1): 39-48, 2006). CIGB-M3 has been developed into a product formulation suitable for clinical studies, and a phase I clinical trial supervised by the Cuban regulatory authorities started in March 2007. The trial involves 20 colorectal cancer patients and two dose levels of the 131I-labeled fragment.
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Patent status |
CU-2002-0086; granted in China, South Korea, Russia and South Africa. |
Project status |
Phase I clinical trial with two different dose levels of the 131I radiolabeled diabody in colorectal carcinoma patients. To the moment, specific tumor binding of the radiolabeled molecule has been shown in all studied patients, with a very high safety profile.
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Type of collaboration requested |
The group that developed the fragments is also interesting in exploring modifications of the CIGB-M3 diabody, and its monomeric counterpart, in order to develop new and more efficient anti-tumor antibodies via their coupling and conjugation with novel radionucleotides, drugs, toxins, and other biomolecules.
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Competitives advantages Milestones |
• Experience in the field of antibody genetic engineering, highly skilled staff, versatility of the technology (cost advantage). Milestones to be developed jointly with the partner.
• A molecule (anti-CEA recombinant multivalent scFv fragment) that has finished successfully the Development phase and has started Phase I human trials.
The phase I CT, to end in 2008, should be followed by phase I/II RIT studies.
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Host Insitutions |
Center for Genetic Engineering and Biotechnology (CIGB). Ave 31, e/158 y 190 Cubanacán, Playa. PO Box 6996, La Habana, 10600, Cuba. Tel. (53-7) 2712397; 2716022. Fax. (53-7) 2736008; 2718070. E-mail: ernesto.lopez@cigb.edu.cu
Web site: http://gndp.cigb.edu.cu
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Project code:
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BIO/CIGB/2008-05
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