Lillian Siu, MD of the Princess Margaret Cancer Centre discusses ESMO 2020 abstract #524O, Proffered Paper: Initial Results of a Phase 1 Study of MK-4830, a First-in-Class Anti-Immunoglobulin-Like Transcript 4 (ILT4) Myeloid-Specific Antibody in Patients (Pts) With Advanced Solid Tumors.
MK-4830, a myeloid-specific ILT4 receptor-targeted antibody given either as a single agent or in combination with pembrolizumab (Keytruda ®; Merck & Co.), was well tolerated and showed positive objective responses in patients with advanced solid tumors who were heavily pre-treated.
This is the inference drawn from the results of a phase I dose-escalation analysis presented during the ESMO Virtual Congress 2020 by Professor Lillian L. Siu, MD, FRCPC, Senior Scientist, Princess Margaret Cancer Centre, Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre at the University of Toronto in Toronto , Canada.
Siu identified MK-4830 in her presentation as a novel, first-in-class human IgG4 monoclonal antibody targeting the myeloid-specific anti-immunoglobulin-like transcript 4 (ILT4) inhibitory immune checkpoint receptor, a transmembrane protein and immunoglobulin-like transcript (ILT) protein family member.
Siu noted that in tumor immune evasion, ILT4 plays a key role. Myeloid cells, including monocytes, macrophages , dendritic cells (DCs) and granulocytes, and some tumor cells, mainly express ILT4. *
Action process
The anti-ILT4 monoclonal antibody MK-4830 targets and binds to ILT4 following administration, which prevents the binding of ILT4 ligands to their receptor and prevents signaling mediated by ILT4. This, in essence, abrogates the tumor microenvironment (TME) immunosuppressive activities of ILT4, stimulates the expression of pro-inflammatory cytokines, including GM-CSF and tumor necrosis factor-alpha (TNFalpha), and enhances the anti-tumor immune response mediated by the cytotoxic T-lymphocyte (CTL).
MK-4830, a myeloid-specific ILT4 receptor-targeted antibody given either as a single agent or in combination with pembrolizumab (Keytruda ®; Merck & Co.), was well tolerated and showed positive objective responses in patients with advanced solid tumors who were heavily pre-treated.
This is the inference drawn from the results of a phase I dose-escalation analysis presented during the ESMO Virtual Congress 2020 by Professor Lillian L. Siu, MD, FRCPC, Senior Scientist, Princess Margaret Cancer Centre, Cancer Clinical Research Unit (CCRU), Princess Margaret Cancer Centre at the University of Toronto in Toronto , Canada.
Siu identified MK-4830 in her presentation as a novel, first-in-class human IgG4 monoclonal antibody targeting the myeloid-specific anti-immunoglobulin-like transcript 4 (ILT4) inhibitory immune checkpoint receptor, a transmembrane protein and immunoglobulin-like transcript (ILT) protein family member.
Siu noted that in tumor immune evasion, ILT4 plays a key role. Myeloid cells, including monocytes, macrophages , dendritic cells (DCs) and granulocytes, and some tumor cells, mainly express ILT4. *
Action process
The anti-ILT4 monoclonal antibody MK-4830 targets and binds to ILT4 following administration, which prevents the binding of ILT4 ligands to their receptor and prevents signaling mediated by ILT4. This, in essence, abrogates the tumor microenvironment (TME) immunosuppressive activities of ILT4, stimulates the expression of pro-inflammatory cytokines, including GM-CSF and tumor necrosis factor-alpha (TNFalpha), and enhances the anti-tumor immune response mediated by the cytotoxic T-lymphocyte (CTL).
Medical research
The MK-4830 Monotherapy and Pembrolizumab Combination (MK-3475) Study in Participants With Advanced Solid Tumors (MK-4830-001)-NCT03564691