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patients showed complete remission of
disease and one showed partial remis-
sion. Most importantly, there were no
signs of toxic effects such as graft-versus-
host disease or cytokine release syn-
drome. “The study has been so safe that
the [US Food & Drug Administration]
has allowed us to move into an outpa-
tient setting,” Rezvani says. The team is
now initiating an international multi-
center study in partnership with Tokyo-
based Takeda.NK unknowns
Despite recent progress toward NK
cell therapies, there are still many un-
answered questions about how the
immune cells function. For example,
why does the normal complement of
NK cells present in the body fail to auto-
matically eliminate all cancer cells in the
first place? One possibility is that cancer
cells find ways to evade NK cells’ detec-tion. “There have been some studies that
[show that] tumor cells can lose [the]
ligands or proteins on the surface that NK
cells normally recognize,” says Kaufman.
In addition to helping the cancer hide
from NK cells, this loss of recognizable
ligands could potentially play a role in the
development of resistance to cell thera-
pies, he adds. “Typically with a one-time
dosing of NK cells, the disease does come
back eventually; it might be months or
years later. Whether that’s due to resis-
tance to the natural killer cells or other
mechanisms, I don’t think we really know.”
It’s also still not clear whether NK
cells will have better luck than T cellsgetting into solid tumors—a harder-
to-reach environment than blood can-
cers. Huntington says he thinks it’s
possible, particularly if researchers
can find the right antigen to target. “I
think that is certainly feasible,” agrees
Kaufman, “but it will take a little bit
more development.”
Even if researchers do overcome these
challenges, Oh says it’s unlikely that NK
cell immunotherapy will entirely supplant
CAR T therapy. Instead, the technologies
might be effective in combination, par-
ticularly as there’s emerging evidence
that “NK cells could produce other fac-
tors to recruit other immune cells that
may actually then further potentiate the
anti-tumor response,” she says. “I could
envision where there may be benefits to
using both together.” gBianca Nogrady is a freelance science
writer based in Sydney, Australia.Unlike T cells, NK cells don’t
need any antigen-specific
priming to provide a thera-
peutic anti cancer effect.