Immuno-Oncology Advances in Applied Cellular Analysis - 16

Advances in Applied Cellular Analysis * Blocking the "Don't Eat Me" Signal on Cancer Cells Lets Phagocytes Clean Up

Tseng, said, "It was completely unexpected
that CD8+ T cells would be mobilized when
macrophages engulfed the cancer cells in
the presence of CD47-blocking antibodies.
Following engulfment of cancer cells,
macrophages activate T cells to mobilize their
own immune attack against cancer."
Most recently, in an article ("CD47-blocking
immunotherapies stimulate macrophagemediated destruction of small-cell lung cancer")
that appeared June 13, 2016 in The Journal of
Clinical Investigation, the Stanford team
extended their work small-cell lung cancer
(SCLC), a highly aggressive subtype of lung
cancer with limited treatment options.
"Disruption of the interaction of CD47 with
SIRPα using anti-CD47 antibodies induced
macrophage-mediated phagocytosis of human
SCLC patient cells in culture," wrote the article's
authors. "In a murine model, administration of
CD47-blocking antibodies or targeted inactiva-

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tion of the CD47 gene markedly inhibited SCLC
tumor growth."
The investigators asserted that CD47 is a genuine immunotherapeutic target for SCLC. They
attributed the therapeutic response partly to
macrophage-mediated phagocytosis, and partly
to the activation of other myeloid immune subsets, including neutrophils and dendritic cells.
CD47 blockade, the investigators suggested,
may initiate adaptive immune responses. "Since
Hu5F9-G4 is under investigation in clinical trials
for human solid malignancies and acute myelogenous leukemia," the investigators suggested,
"our findings provide scientific justification for
further evaluation of CD47-blocking therapies
in patients with SCLC."
The lead Stanford investigator, Dr. Weissman, is a
founding member of Forty Seven, a clinical-stage
immuno-oncology company that is developing
Hu5F9-G4. Early in 2016, Forty Seven announced
that it has completed the first half of a commit-

ted $75 million Series A financing round and has
licensed the rights to multiple immuno-oncology
programs from Stanford University.
As noted above, in preclinical models, Hu5F9-G4
facilitated phagocytosis and elimination of cancer
cells from multiple human tumor types as a monotherapy. Additionally, when used in combination
therapy, it engaged macrophages as effector cells
to enhance the efficacy of cancer-specific antibodies via antibody-dependent cellular phagocytosis
(ADCP). Importantly, Hu5F9-G4 also could prime
an effective antitumor T-cell response through
cross-presentation of cancer cell antigens by macrophages, preventing engraftment of tumors expressing a cross-presented antigen into animals.
"Targeting CD47 integrates the adaptive and innate immune systems," said Dr. Weissman. "It creates
synergy with existing cancer-specific antibodies like
rituximab, cetuximab, and trastuzumab through
ADCP, and potentially with T-cell checkpoint
inhibitors through cross-presentation." n
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Immuno-Oncology Advances in Applied Cellular Analysis

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