Table 2 Strategies to overcome current clinical challenges associated with CAR T cell therapies.

IssueStrategyExpected outcome
Cytokine release
syndrome (13, 61)
Tocilizumab, siltuximab,
JAK kinase inhibitors,
Blocking IL-6 effects
rapidly reverses fevers,
hypotension, and hypoxia
Development of anti-CAR
idiotypic antibodies
to murine scFvs
Use humanized scFv (62)Longer persistence of
CAR T cells
Lack of persistence of
CAR T cells
Understand mechanisms of
signaling domains that
impart increased longevity
(63); use sorted memory
or stem cells (64)
Long-term persistence
of CAR T cells when
desired by clinical
Relapse owing to loss of
CD19 epitope
Target CD22 and CD19Combinatorial surface
targeting prevents
escape (23)