MCLA-117
is a full length human CLEC12AxCD3 bispecific immunoglobulin G (IgG) that incorporates CH2
region amino acid substitutions to abrogate Fcγ receptor and C1q interactions
while retaining its binding to FcRn. MCLA-117 binds to CD3, a cell-surface molecule
present on all T cells, and CLEC12A, a cell surface molecule present on Acute
Myleoid Leukemia (AML) cells and stem cells. MCLA-117 is designed to recruit
and activate T-cells to kill CLEC12A-expressing AML tumor cells and stem cells,
which may prevent recurrence of tumors. MCLA-117 redirects patient's cytotoxic
T cells to induce AML tumor lysis.
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| New Drug for Treatment for Acute Myleoid Leukemia |
MCLA-117
is a human full length IgG1 bispecific antibody that uses an IGKV1-39/IGKJ1
common light chain (cLC) together with anti-CLEC12A-specific VH and an
anti-CD3-specific VH. The Fc portion of MCLA-117 was engineered to selectively
facilitate heavy chain heterodimerization and to abrogate Fcγ receptor and
C1q-mediated effector function. The MCLA-117 affinity for CLEC12A is 60-fold
greater than for CD3, 3 nM vs 177 nM respectively, which is predicted to
facilitate the preferential opsonization of the AML blasts with MCLA-117.
What is CLEC12A?
CLEC12A
is a myeloid differentiation antigen that is expressed on 90-95% of newly
diagnosed and relapsed AML. Moreover, CLEC12A is selectively expressed on
leukemic stem cells (LSCs) but not normal early hematopoietic progenitors,
including hematopoietic stem cells (HSCs).
Dosages and Approvals:
MCLA-117
is being developed by Merus pharmaceuticals, and it is presently in Phase I/II
stage [1, 2]. In preclinical studies, MCLA-117 has been shown to recruit and activate the immune system’s own T-cells to kill AML tumor cells and stem cells.
References:
1. Van
Loo, P. F.; et. al. Preclinical
Evaluation of MCLA117, a CLEC12AxCD3 Bispecific Antibody Efficiently Targeting
a Novel Leukemic Stem Cell Associated Antigen in AML. Blood 2015, 126, 325. (free article)
2. ClinicalTrials.gov A Phase 1,
Multinational Study of MCLA-117 in Acute Myelogenous Leukemia. NCT03038230
