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Updated: Aug 18, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Adenoviruses for treatment of cancer
Anna Kanerva1, Akseli Hemminki
1Cancer Gene Therapy Group, Rational Drug Design, Biomedicum Helsinki, University of Helsinki, Finland.
Abstract:
Most cases of cancer, when detected at an advanced stage, cannot be cured with conventional therapeutic modalities. Therefore, novel targeted approaches such as gene therapy are needed. Nevertheless, while the safety record of gene therapy for cancer has been excellent with more than a thousand patients treated without mortality related to the therapy, clinical efficacy has so far been limited. Moreover, it has become evident that clinical efficacy is partly determined by efficacy of gene delivery. Most adenoviruses used for gene therapy have been based on serotype 5 (Ad5). Unfortunately, recent data suggest that the primary receptor, the coxsackie-adenovirus receptor (CAR) expression in tumors may be highly variable resulting in resistance to adenovirus infection. Consequently, various strategies have been evaluated to modify adenovirus tropism in order to circumvent CAR deficiency, including retargeting complexes or genetic capsid modifications. To further improve tumor penetration and local amplification of the anti-tumor effect, selectively oncolytic agents, e.g. conditionally replicating adenoviruses (CRAds), have been constructed. Infection of tumor cells results in replication, oncolysis, and subsequent release of the virus progeny. Normal tissue is spared due to lack of replication. This review will focus on a discussion of various modifications of adenovirus to achieve efficient anti-tumor effect, and special emphasis will be placed on CRAds in multimodality treatments.
Insights
Gene therapy for cancer shows excellent safety but limited efficacy due to variable tumor cell targeting. Modifications to adenoviruses, including conditionally replicating adenoviruses (CRAds), aim to improve tumor penetration and therapeutic outcomes.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Advanced-stage cancers often resist conventional treatments, necessitating novel therapeutic strategies like gene therapy.
- Adenovirus-based gene therapy for cancer has a strong safety profile but faces challenges in clinical efficacy, largely due to limitations in gene delivery.
- Variable expression of the coxsackie-adenovirus receptor (CAR) on tumor cells can lead to resistance against conventional adenovirus vectors.
Purpose of the Study:
- To review modifications of adenoviruses aimed at enhancing anti-tumor effects in cancer gene therapy.
- To emphasize the role of conditionally replicating adenoviruses (CRAds) in multimodality cancer treatments.
Main Methods:
- Discussion of strategies to modify adenovirus tropism, including retargeting complexes and genetic capsid modifications, to overcome CAR deficiency.
- Exploration of selectively oncolytic agents, specifically CRAds, designed for tumor cell replication and oncolysis.
- Review of adenovirus modifications to improve tumor penetration and amplify local anti-tumor effects.
Main Results:
- Adenovirus modifications are being evaluated to circumvent CAR deficiency and improve gene delivery efficacy.
- Conditionally replicating adenoviruses (CRAds) demonstrate potential for selective tumor cell infection, replication, and oncolysis, sparing normal tissues.
- Engineered adenoviruses offer improved prospects for enhanced anti-tumor activity in cancer treatment.
Conclusions:
- Adenovirus modifications, particularly CRAds, are crucial for overcoming gene delivery challenges and improving the efficacy of gene therapy for cancer.
- CRAds represent a promising approach for multimodality cancer treatments, enhancing tumor-specific effects.
- Further development of modified adenoviruses holds significant potential for advancing targeted cancer therapies.
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