PHCbi-Panasonic eBook - 35

Cell Therapy Today * New Developments in Immunotherapy * CAR-Engineered Blood Stem Cells Offer New Hope for Long-Term HIV Gene Therapy

persisted for nearly two years. The CAR-expressing
HSPCs also expanded in response to SHIV infection
and differentiated into SHIV-targeting effector T
cells. Interestingly, the level of CAR T-cell response
mirrored the SHIV antigen level. "Intriguingly,
we found that CAR cells contracted during cART
treatment during lower levels of antigen expression, followed by a rapid expansion after cART
withdrawal, mimicking a memory response,"
the team writes. "As a result, CAR animals had
decreased viremia during post-cART viral rebound
as compared to control animals."

lymph nodes, gut, and brain. "These results set
the stage for future attempts to eradicate viral
infection and provide more effective immune
surveillance for HIV, using optimized CAR vectors
and combinatorial approaches," the team notes.
" ... we demonstrate that HIV/SHIV-specific CAR
cells possess strong antiviral activity even at low
levels....These cells should act as sentinels, generating a robust immune response to reactivated
infected cells months or years after they are introduced, without requiring expression in a high
percentage of immune cells."

Encouragingly, the CAR cells were found in
multiple lymphoid tissues, including those of
the gut, which is a major site for HIV replication
and persistence, and there was no evidence of
toxicity associated with the treatment. Compared
with control animals, macaques transplanted
with the autologous CAR-engineered HSPCs
exhibited much lower SHIV mRNA levels in the

The researchers say that while their studies could
also lay the foundation for the development of
CAR-engineered HSPCs against other diseases,
"Importantly, these findings have broad implications beyond HIV. Additional preclinical studies
should be performed to explore HSPC-expressed
CARs against other infectious diseases and cancer
in greater detail." n

35

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PHCbi-Panasonic eBook

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