Activating innate immunity in a controlled manner is
necessary
for the development of next-generation therapeutics. Adjuvants, or
molecules that modulate the immune response, are critical components
of vaccines and immunotherapies. While small molecules and biologics
dominate the adjuvant market, emerging evidence supports the use of
immunostimulatory polymers in therapeutics. Such polymers can stabilize
and deliver cargo while stimulating the immune system by functioning
as pattern recognition receptor (PRR) agonists. At the same time,
in designing polymers that engage the immune system, it is important
to consider any unintended initiation of an immune response that results
in adverse immune-related events. Here, we highlight biologically
derived and synthetic polymer scaffolds, as well as polymer–adjuvant
systems and stimuli-responsive polymers loaded with adjuvants, that
can invoke an immune response. We present synthetic considerations
for the design of such immunostimulatory polymers, outline methods
to target their delivery, and discuss their application in therapeutics.
Finally, we conclude with our opinions on the design of next-generation
immunostimulatory polymers, new applications of immunostimulatory
polymers, and the development of improved preclinical immunocompatibility
tests for new polymers.