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THE CELL AND GENE THERAPY MARKET IN ONCOLOGY is $1,582M

MARKET SIZE: The global market for cell and gene therapy for oncology reached $1,582 million in 2020 and is expected to climb to $2,744 for 2021.

There are over 100 different types of cancer; some of the more prominent include lung, breast, brain, blood, prostate and colon cancer. The immune system plays a primary role in the body’s defense against malignancy. Although a tumor is derived from the body’s own cells and is expected to possess proteins that are recognized as self and nonantigenic, neoplastic cells can express antigens that are not recognized as self. These cells can often be eliminated by the immune system.

FORECAST: projected to increase to $7,391 in 2025; $17,490 million by 2030.

Treating cancer is difficult because it is not a single disease and because all the cells in a single tumor do not behave in the same way. Although most cancers are thought to be derived from a single abnormal cell, by the time a tumor reaches a clinically detectable size, the cancer may contain a diverse population of cells.

Market Forecast:  Strong increases in the CAR-T therapy market, increasing from just $16 million in 2017 to $1,081 million in 2020 and projected to increase to $7,391 in 2025; $17,490 million by 2030.  Blood cancers are the leading driver in the segment, representing 68% of total sales. This is expected to be the primary segment through the forecast, representing 80% of sales by 2025 and 80% in 2030.  The United States and Europe are the largest markets due to overall product approvals and cost associated with the therapies. The US market represented nearly 77%, while Europe represented 19% in 2020.  Gilead and Novartis combined represent 68% of the market for cell and gene therapy in oncology.  Industry refocuses on oncology cell and gene therapies in a post-pandemic arena, returning to pre-pandemic growth.

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AAV CAPSID DISCOVERY UPDATE

Adeno-associated viruses (AAV) are small human viruses which provoke only a mild immune response and are not known to cause any human disease. AAVs are quite simple in organization, possessing a small (4.7kb) single-stranded DNA genome with only two open reading frames (ORFs), rep and cap, flanked by short (145 base) inverted terminal repeats (ITRs). The rep ORF encodes multiple overlapping sequences for proteins required for replication, and the cap ROF does the same for capsid proteins, which are the proteins forming the outer viral protein coat. These genes alone are not sufficient for viral replication, and AAVs require co-infection with a second, helper virus (such as an adenovirus or HSV) to supply the remaining gene products for replication (hence the name adeno-associated virus).

Gene therapy AAV vectors are further modified to remove the rep and cap genes from the viral genome (along with their promoters and polyadenylation signal), replacing them with a therapeutic expression cassette. Production of recombinant AAV vectors in cell lines requires the rep and cap genes to be supplied by a plasmid transfected in trans, in addition to the genes supplied by the helper virus. None of these externally supplied viral genes are packaged into the final construct, so the resulting viral delivery vehicle consists only of the therapeutic cassette encased in an AAV capsid, without any viral genes present. The gene therapy vector is therefore incapable of replication, even with co-infection by a suitable helper virus.
In addition to their safety, AAV vectors possess many features which make them attractive gene therapy candidates. They have extremely low immunogenicity, they can infect both dividing and non-dividing cells, and they can persist outside the genome to offer stable, long-term expression without the risks associated with host genome integration.

AAV vectors also suffer from several shortcomings, however:
• Because of their wide distribution, many individuals have already been exposed to naturally occurring AAV serotypes and produce immune responses against them.
• AAV vectors cannot reach most tissues efficiently, and do not spread easily within those tissues if they do.
• Vectors will preferentially target some cell types but not others.
• Transduction efficiency is often extremely low.

Each of these shortcomings can be addressed by innovations in capsid structure. In addition to protecting the DNA payload, the capsid is responsible for binding to specific receptors on the target cell and safely delivering the DNA payload to the cell machinery that so will be transported to the nucleus. Viral packaging efficiency, host immunological response, tissue and cell type specificity, and transduction efficiency are all determined by the capsid serotype. Unfortunately, initial gene therapy experiments were restricted to a handful of natural AAV serotypes which had limited tropism in many human cell types. Common serotypes also present problems with pre-existing immunity (PEI), as up to 90% of the human population have already been exposed to at least one AAV serotype. For these reasons, novel capsid discovery is a current hotbed of gene therapy research.

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