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The use of oncolytic virus therapy for myeloma shows considerable promise in pre-clinical models

The use of oncolytic virus therapy for myeloma shows promise based on pre-clinical models. This therapy leverages the unique tropism of viruses for targeting tumor cells, inducing cell death through intrinsic and extrinsic pathways. The FDA-approved T-VEC, an adenovirus, has shown efficacy in a variety of cancers, showcasing the potential of oncolytic virotherapy. Specifically, Myeloma-Specific Adenovirus ADCE1A targets myeloma cells with minimal impact on healthy cells, demonstrating potent cell death induction in both myeloma and melanoma cells. Preliminary studies suggest an additive effect when ADCE1A is combined with standard chemotherapies, emphasizing its potential as a complementary treatment option. Future research aims to explore the efficacy of ADCE1A in vivo in combination with existing therapies, targeting dormant/resistant myeloma cells, and optimizing viral delivery mechanisms.

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The use of oncolytic virus therapy for myeloma shows considerable promise in pre-clinical models

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  1. The use of oncolytic virus therapy for myeloma shows considerable promise in pre-clinical models • Miss Georgia Stewart • Sheffield Myeloma Research Team • Department of Oncology and Metabolism • Faculty of Medicine Dentistry and Health • University of Sheffield, UK

  2. Oncolytic Virotherapy Most Viruses have a preferential tropism for tumour cells Intrinsic and extrinsic cell death Over 48 clinical trials using DNA and RNA viruses in a range of cancers T-VEC: First FDA approved oncolytic virus

  3. Adenovirus Naturally lytic life cycle Many serotypes Broad cell tropism Large amount of nonessential genes Can cause clinical disease- generally self limiting

  4. Adenovirus ARF MDM2 E2F Rb p53 Apoptosis Targeted for destruction Cell Cycle E1B 55K/ E4 orf6 E1A Viral Replication

  5. Myeloma-Specific Adenovirus Myeloma Cells ADCE1A CS1 E1A Myeloma-specific promoter Healthy Cells

  6. CS1 is ovrerexpressed in myeloma cell lines IgG Anti-CS1 CS1+ve

  7. ADCE1A Induced Potent Cell Death in Myeloma Cells 4 Days After infection Myeloma Melanoma

  8. ADCE1A Induced Potent Cell Death in Primary CD138+ Cells After 4 Days

  9. ADCE1A Has No Impact on Normal Bone Microenvironment Cells

  10. ADCE1A Induces Cell Death Via an Apoptotic Independent Mechanism

  11. ADCE1A in vivo in a high tumour burden model Treatment IV (2x/wk) Bones Flushed and Analysed U266 IV (1x106) 5 weeks 3 weeks PBS

  12. ADCE1A Significantly Reduces Tumour Burden in U266 Xenografts

  13. ADCE1A and bortezomib combination therapy prevents cell line recovery

  14. ADCE1A and Bortezomib have an additive effect in vitro

  15. ADCE1A and Lenalidomide have an additive effect in vitro

  16. ADCE1A effectively replicates in, and kills myeloma cells and primary cells Mechanism of cell death is unclear ADCE1A shows efficacy in vivo ADCE1A stops cell line regrowth in vitro ADCE1A shows an additive effect in vitro with standard chemotherapies Summary

  17. Future Work • Test ADCE1A in combination with standard therapies in vivo • Test ADCE1A in dormant/resistant myeloma cells • Optimise viral delivery mechanisms

  18. Dr Simon Tazzyamn Dr Andrew Chantry Dr MunittaMuthana Dr Shelly Lawson Darren Lath Holly Evans Jenny Down Jack Harrision Beverly King Dan Holligan Acknowledgements

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