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Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models
Published on: March 13, 2018
Cancer gene therapy--first international conference. 8-9 July 1999, Hammersmith Hospital, London, UK
1Current Drugs Ltd, Middlesex House, 34-42 Cleveland Street, London W1P 6LB, United Kingdom. tamaraz@cursci.co.uk
Abstract:
The failings of the cancer gene therapies that have so far been tested in clinical trials are that they do not reach sufficient target cells and are not toxic enough. The eventual success of many strategies may also depend on their ability to elicit a strong antitumor immune response. Unsurprisingly, therefore, the focus of this meeting, the first of the International Society of Cancer Gene Therapy, was on new strategies currently in preclinical development that address these problems, and relatively little new clinical information was presented. There was much interest in a new class of therapeutic genes, those encoding fusogenic membrane glycoproteins, which are very toxic and have the potential to elicit a potent bystander effect and a strong immunogenic response. The aim of another strategy that shows considerable promise is to improve the toxicity of replication-conditional adenoviruses by replacing deleted adenoviral genes with cytotoxic or suicide genes. Disappointingly, there was little discussion of new vector systems that might improve gene delivery. The most exciting development in ex vivo immunogene therapies presented was progress towards the development of a streamlined 'off the shelf' immunogene therapy for relapsing leukemia patients who have undergone bone marrow transplants. In addition, a few promising immunotherapies were discussed that may provide several starting points for the development of new gene therapies that are effective in eliciting tumor immunogenicity.
Insights
New cancer gene therapies focus on improving cell targeting and toxicity. Promising preclinical strategies include fusogenic glycoproteins and modified adenoviruses to enhance antitumor immune responses.
Area of Science:
- Oncology
- Gene Therapy
- Immunotherapy
Background:
- Current cancer gene therapies face challenges with insufficient target cell delivery and suboptimal toxicity.
- Effective cancer gene therapy may require a robust antitumor immune response.
Purpose of the Study:
- To highlight novel preclinical cancer gene therapy strategies addressing current limitations.
- To discuss advancements in gene delivery, toxicity enhancement, and immunogenicity.
Main Methods:
- Focus on preclinical research and emerging therapeutic gene classes.
- Investigation of fusogenic membrane glycoproteins for enhanced toxicity and immune response.
- Modification of replication-conditional adenoviruses with cytotoxic or suicide genes.
Main Results:
- Fusogenic glycoproteins show high toxicity and potential for bystander and immune effects.
- Modified adenoviruses aim to increase toxicity by incorporating cell-killing genes.
- Progress in developing 'off-the-shelf' ex vivo immunogene therapy for leukemia.
Conclusions:
- Preclinical strategies show promise in overcoming cancer gene therapy hurdles.
- Enhanced toxicity and immunogenicity are key areas of development.
- Advancements in ex vivo immunogene therapy offer new hope for leukemia patients.
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