Adoptive T-cell therapy engineered to express membrane-anchored, tumor-targeted interleukin-12 (IL-12) to localize IL-12 signaling at the T-cell/tumor interface, drive Th1 activation, enhance CD8+ T-cell cytotoxicity and IFN-γ production, and modulate the tumor microenvironment.
Engineered adoptive T cells expressing membrane-anchored, tumor-targeted interleukin-12 (IL-12) that localizes IL-12 signaling at the T cell–tumor interface via binding cell-surface vimentin (CSV). This drives Th1 polarization, enhances CD8+ T-cell cytotoxicity and IFN-gamma production, activates NK cells, and reprograms the tumor microenvironment to promote immune-mediated tumor cell killing while limiting systemic IL-12 exposure and toxicity.
YES
INDIRECT
Membrane-anchored, CSV-targeted IL-12 localizes cytokine signaling at CSV+ tumor cells, boosting Th1 responses and enhancing CD8+ T-cell and NK-cell cytotoxicity (perforin/granzyme, Fas/FasL, IFN-γ), leading to immune-mediated killing; CSV binding itself does not directly lyse cells.
Adoptive T-cell therapy engineered to express membrane-anchored, tumor-targeted interleukin-12 (IL-12) to localize IL-12 signaling at the T-cell/tumor interface, drive Th1 activation, enhance CD8+ T-cell cytotoxicity and IFN-γ production, and modulate the tumor microenvironment.
Engineered adoptive T cells expressing membrane-anchored, tumor-targeted interleukin-12 (IL-12) that localizes IL-12 signaling at the T cell–tumor interface via binding cell-surface vimentin (CSV). This drives Th1 polarization, enhances CD8+ T-cell cytotoxicity and IFN-gamma production, activates NK cells, and reprograms the tumor microenvironment to promote immune-mediated tumor cell killing while limiting systemic IL-12 exposure and toxicity.
NO
INDIRECT
Anchored IL-12 binds IL-12 receptors (including IL12RB1) on T/NK cells to activate them; the activated effectors kill CSV-positive tumor cells, not the IL-12 receptor–expressing cells.
Adoptive T-cell therapy engineered to express membrane-anchored, tumor-targeted interleukin-12 (IL-12) to localize IL-12 signaling at the T-cell/tumor interface, drive Th1 activation, enhance CD8+ T-cell cytotoxicity and IFN-γ production, and modulate the tumor microenvironment.
Engineered adoptive T cells expressing membrane-anchored, tumor-targeted interleukin-12 (IL-12) that localizes IL-12 signaling at the T cell–tumor interface via binding cell-surface vimentin (CSV). This drives Th1 polarization, enhances CD8+ T-cell cytotoxicity and IFN-gamma production, activates NK cells, and reprograms the tumor microenvironment to promote immune-mediated tumor cell killing while limiting systemic IL-12 exposure and toxicity.
NO
INDIRECT
Membrane-anchored IL-12 on the engineered T cells binds IL-12 receptors (including IL12RB2) on immune cells to activate them; the activated T/NK cells then kill CSV-expressing tumor cells via perforin/granzyme and IFN-gamma–mediated mechanisms. Cells expressing IL12RB2 are activated, not directly killed.
Humanized anti-HER2 IgG1 monoclonal antibody that inhibits HER2 signaling and dimerization, promotes receptor downregulation, and mediates ADCC via Fcγ receptor–bearing NK cells.
Humanized anti-HER2 IgG1 monoclonal antibody that binds HER2, blocks receptor dimerization and downstream signaling, promotes receptor internalization/downregulation, and triggers antibody-dependent cellular cytotoxicity via Fc gamma receptor–bearing NK cells, inhibiting proliferation of HER2-overexpressing tumor cells.
YES
DIRECT
Trastuzumab binds HER2 on target cells and its Fc region engages Fcγ receptors on NK cells (and other effectors) to trigger antibody‑dependent cellular cytotoxicity (ADCC), killing HER2-expressing cells; complement-mediated cytotoxicity may also contribute.
Humanized anti-HER2 IgG1 monoclonal antibody that inhibits HER2 signaling and dimerization, promotes receptor downregulation, and mediates ADCC via Fcγ receptor–bearing NK cells.
Humanized anti-HER2 IgG1 monoclonal antibody that binds HER2, blocks receptor dimerization and downstream signaling, promotes receptor internalization/downregulation, and triggers antibody-dependent cellular cytotoxicity via Fc gamma receptor–bearing NK cells, inhibiting proliferation of HER2-overexpressing tumor cells.
NO
INDIRECT
CD16A+ NK cells are not killed. Trastuzumab binds HER2 on tumor cells and its Fc engages CD16A to activate NK-cell ADCC, killing HER2-overexpressing tumor cells.