Trillium Therapeutics Inc (TRIL)

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Antibody Therapy Targeting CD47 and CD271
Effectively Suppresses Melanoma Metastasis
in Patient-Derived Xenografts

http://www.cell.com/cell-reports/pdf/S2211-1247(16)30890-7.pdf

SUMMARY
The high rate of metastasis and recurrence among
melanoma patients indicates the existence of cells
within melanoma that have the ability to both initiate
metastatic programs and bypass immune recognition.
Here, we identify CD47 as a regulator of
melanoma tumor metastasis and immune evasion.
Protein and gene expression analysis of clinical melanoma
samples reveals that CD47, an anti-phagocytic
signal, correlates with melanoma metastasis.
Antibody-mediated blockade of CD47 coupled with
targeting of CD271+ melanoma cells strongly inhibits
tumor metastasis in patient-derived xenografts. This
therapeutic effect is mediated by drastic changes
in the tumor and metastatic site immune microenvironments,
both of whichwhich exhibit greatly
increased density of differentiated macrophages
and significantly fewer inflammatory monocytes,
pro-metastatic macrophages (CCR2+
/VEGFR1+
),
and neutrophils, all of which are associated with disease
progression. Thus, antibody therapy that activates
the innate immune response in combination
with selective targeting of CD271+ melanoma cells
represents a powerful therapeutic approach against
metastatic melanoma.