Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 325

As for assessing the risk of HSRs mediated by C, to our
knowledge, the only direct approaches are the in vitro C activation
measurements in normal human sera (NHS), the in vivo porcine and
canine CARPA tests and the basophil leukocyte activation-based
allergenicity assays, provided mostly as services by a few contract
research organizations (CROs). A combination of these tests can
predict in a rough, semiquantitative way the likely presence, severity
and frequency of CARPA caused by a certain drug in most people,
and also in individual patients. The unique benefit of the large
animal (pig and dog) model of CARPA is that the endpoints, i.e.,
cardiopulmonary and hematological changes, when they occur, not
only reveal the potential reactogenicity of the drug, but also model
the physiological changes occurring in hypersensitive individuals. As
mentioned in the text above (Table 11.5), liposome-induced CARPA
in pigs and dogs provides a model of the infusion reactions seen in
hypersensitive individuals. Focusing on liposomes, the C and CARPA
tests are useful in assessing their risk of causing HSRs, enabling
early abandonment of highly reactogenic formulations. For lack of
a valid animal model for assessing the immunogenicity of human or
humanized protein containing liposomes, securing of immune safety
of these products seems to be an even greater challenge than solving
the HSR problem.
What gives hope in this challenging “terra nova” is that interest
will never cease in improving the therapeutic efficacy of available
drugs, or creating new drugs whose molecular buildup gets
increasingly complex. Hopefully it is not too far in the future that
we can equip liposomes and other drug carrier nano-systems with
immune evasive capabilities, and/or “teach” the immune system to
distinguish these nanotech marvels from harmful viruses or other
nano-organisms.
Acknowledgments
The authors gratefully acknowledge the financial support by the
Barenholz Fund and the National Office for Research and Technology
(NKTH), Budapest (CARPA777,NANOMEDI and TÁMOP-4.2.1.B-
09/1/KMR-2010-0001 and 4.1.2.B-10/2/KONV-2010-0001, with
support by the European Union, co-financed by the European Social
Fund).