RE: Vaccines28 Feb 2026 21:34
- Modi-1 Vaccine: This vaccine targets citrullinated proteins. Durrant's team found that it induces potent CD4 T-cell responses that recognize tumours expressing IFN-γ-inducible MHC class II, effectively making "cold" tumours visible to the immune system.
- ImmunoBody® Platform: Her development of DNA vaccines (like SCIB1) aims to stimulate high-avidity T cells that secrete elevated levels of IFN-γ to directly induce apoptosis in target cancer cells.
"Cold" tumors hide from T cells by losing MHC-I (like going invisible). ANKTIVA (IL-15 drug) wakes up natural killer (NK) cells to attack these hidden cancer cells. The NK cells release IFN-gamma, which forces the tumor to show MHC-I again → turns "cold" into a "hot" tumor. Now T cells can see & attack it too, plus it builds long-term memory T cells for ongoing protection.
A key strategy for many solid tumors is to hide from T cells by reducing or losing MHC-I molecule expression, a mechanism addressed by Scancell's Moditope® and ImmunoBody® platforms.
The Problem: Cold Tumors and MHC-I Loss
Immune Escape: To survive, tumors often downregulate or lose MHC-I antigen presentation, making them "invisible" to CD8+ T cells.
"Cold" Tumors: These tumors (often with low mutational load) exhibit low MHC-I and low PD-L1 expression, causing them to be unresponsive to traditional checkpoint inhibitors.
Mechanism of Loss: Tumor cells can lose MHC-I through genetic mutations (e.g., in $eta$2M) or by increasing lysosomal degradation of MHC-I molecules.
Scancell’s Solutions to Escape Mechanisms
Scancell's platforms are designed to target and overcome these evasion tactics:
Moditope® (Modi-1 Vaccine):
Mechanism: Targets stress-induced post-translational modifications (siPTMs) such as citrullination.
Overcoming MHC-I Loss: Modi-1 stimulates CD4+ T cells rather than CD8+ T cells. When activated, these CD4+ T cells infiltrate the tumor and release interferon-gamma (IFN
), which induces the upregulation of MHC Class II on tumor cells, exposing them to attack.
Indications: Currently in Phase I/II trials (ModiFY) for hard-to-treat "cold" tumors like triple-negative breast cancer, ovarian cancer, and head and neck cancer.
ImmunoBody®:
Mechanism: This DNA-based platform produces antibodies that bind to tumor antigens, creating immune complexes that are taken up by dendritic cells
T Cell Activation: This leads to the generation of high-avidity T cells designed to kill tumor cells.
Lead Program: SCIB1 is being developed for melanoma.
GlyMab® (Anti-glycan antibodies):
Mechanism: These antibodies target specific glycans (sugars) added to proteins or lipids on the surface of cancer cells, which are not subject to the same MHC-I loss evasion mechanisms.
Summary of Approach
Scancell's strategy, particularly with the Moditope platform, is to bypass the need for MHC-I by utilizing CD4+ killer T cells, effectively turning "cold" tumors into "hot" (inflamed) ones and making them visib
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