Take five in T-cell lymphoma
The recent granting of orphan drug designation to March Biosciences' lead asset, MB-105, highlights the fact that treating T-cell lymphomas with cell therapies still lags behind that of B-cell malignancies. MB-105 is an autologous Car-T therapy against CD5, an antigen said to be expressed on T cells and thus, in theory, a promising target for cancers involving these cells. But a major problem is so-called fratricide, meaning the destruction not only of the target cells but also of the Car-T cells, which naturally also express CD5. MB-105 cells, however, were found to degrade CD5 and thus avoid such self-killing, according to a preclinical presentation at ASCO 2023. Other companies developing anti-CD5 cell therapies, including Iaso and Vittoria, purposely edit out CD5 during manufacturing, the former using Crispr. Others still employ a different cell type, such as NK cells, which don't normally express CD5. While March is testing MB-105 in phase 2 for CD5-positive T-cell lymphoma, for which orphan drug designation was granted, MB-105 is also in phase 1 in T-cell leukaemias.
Anti-CD5 cell therapies
| Project | Mechanism | Company | Status | How fratricide is avoided |
|---|---|---|---|---|
| MB-105 | CD5 Car-T | March Biosciences | Ph2 in CD5+ve T-cell lymphoma | CD5 is degraded on Car-T cells |
| EB-BH2026 | CD5/CD7 Car-T | Essen Biotech | Ph1/2 in ALL | Not applicable (not being studied in a T-cell malignancy) |
| AB-205/ GCC2005 | CD5 CAR-NK | Artiva (GC Cell) | Ph1 in CD5+ve T-cell & NK cell malignancies | Not applicable (uses NK rather than T cells) |
| CD5 CART | CD5 Car-T | Yake Biotechnology | Ph1 in CD5+ve T-cell non-Hodgkin lymphoma | Unclear |
| Senza5 CART5 | CD5 Car-T | Vittoria Biotherapeutics | Ph1 in CD5+ve peripheral T-cell lymphoma | CD5 is deleted during manufacturing |
| CT125A | CD5 Car-T | Iaso Biotherapeutics | Ph1 in CD5+ve haematopoietic malignancies | CD5 is knocked out via Crispr/Cas9 during manufacturing |
| ICG124 | CD5 Car-T (IL-15 expressing) | iCell Gene | Ph1 in T-cell malignancies | Unclear |
| MT-101 | CD5 Car-macrophage | Myeloid Therapeutics | Ph1/2 in CD5+ve T-cell lymphoma SUSPENDED | Not applicable (uses macrophages rather than T cells) |
| CRC-03 | CD5 Car-T | Curocell | Preclinical | CD5 is downregulated using a shRNA cassette |
Source: OncologyPipeline.
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