beta-ray-emitting radioisotopes. Beside therapeutic responses, immune responses to
these therapeutic radioisotope-labeled nanomaterials might be modified by the
radioactivity. This radioactivity might destroy tissue macrophages such as Kupffer
cells and/or change the response of immune cells of innate immunity (Kupffer cells
of hepatic sinusoid or MZMUs of the spleen) or even immune cells of adaptive
immunity (mDC of space of Disse of the liver or MMMUs of the spleen) [26, 45].
Though anti-PEG IgM antibody was developed against PEG coating the nanomaterials at second injection of the PEGylated nanomaterials, and blood clearance was
accelerated concordantly [49], we are not sure that IgM response of adaptive
immunity is the unique aspect of this trained memory response. We need to remind
that innate immune responses can also be trained and thus be enhanced at second
injection [3], and the cells involved in innate and adaptive responses are often
overlapped implying the concomitant activation of the downstream immune activation [2]. Considering all these phenomena of bodily immune responses to therapeutic radioisotope-labeled PEGylated nanomaterials, what we need to get is how
much of the injected materials are reaching the targets while other innate or
adaptive immune organs are responding to the collateral accumulation of the same
therapeutic materials. Further to this, how much amount of radioactivity should be
given to the patients should also be elucidated using the preclinical PET/SPECT
imaging and individualized dosimetry. Understanding the fate of radionanomedicines made of radiolabeled nanomaterials in human will be feasible
referring all the facts and principles of innate immunity as well as adaptive
immunity and physiology unique to the human being.
References
1. L.L. Lanier, Shades of grey–the blurring view of innate and adaptive immunity. Nat. Rev.
Immunol. 13(2), 73–74 (2013)
2. E. Vivier, D.H. Raulet, A. Moretta, M.A. Caligiuri, L. Zitvogel, L.L. Lanier et al., Innate or
adaptive immunity? The example of natural killer cells. Science 331(6013), 44–49 (2011)
3. M.G. Netea, L.A. Joosten, E. Latz, K.H. Mills, G. Natoli, H.G. Stunnenberg et al., Trained
immunity: a program of innate immune memory in health and disease. Science 352(6284),
aaf1098 (2016)
4. A. Doni, C. Garlanda, A. Mantovani, Innate immunity, hemostasis and matrix remodeling:
PTX3 as a link. Semin. Immunol. 28(6), 570–577 (2016)
5. X. Cao, Self-regulation and cross-regulation of pattern-recognition receptor signalling in
health and disease. Nat. Rev. Immunol. 16(1), 35–50 (2016)
6. S.Y. Seong, P. Matzinger, Hydrophobicity: an ancient damage-associated molecular pattern
that initiates innate immune responses. Nat. Rev. Immunol. 4(6), 469–478 (2004)
7. D. Gao, W. Li, Structures and recognition modes of toll-like receptors. Proteins 85(1), 3–9
(2017)
8. N. Nakamoto, T. Kanai, Role of toll-like receptors in immune activation and tolerance in the
liver. Front. Immunol. 5, 221 (2014)
9. J.D. Jones, R.E. Vance, J.L. Dangl, Intracellular innate immune surveillance devices in plants
and animals. Science 354(6316), 1117 (2016)
10. J. Zhu, W.E. Paul, CD4 T cells: fates, functions, and faults. Blood 112(5), 1557–1569 (2008)
404
D. S. Lee and Y. K. Shin
these therapeutic radioisotope-labeled nanomaterials might be modified by the
radioactivity. This radioactivity might destroy tissue macrophages such as Kupffer
cells and/or change the response of immune cells of innate immunity (Kupffer cells
of hepatic sinusoid or MZMUs of the spleen) or even immune cells of adaptive
immunity (mDC of space of Disse of the liver or MMMUs of the spleen) [26, 45].
Though anti-PEG IgM antibody was developed against PEG coating the nanomaterials at second injection of the PEGylated nanomaterials, and blood clearance was
accelerated concordantly [49], we are not sure that IgM response of adaptive
immunity is the unique aspect of this trained memory response. We need to remind
that innate immune responses can also be trained and thus be enhanced at second
injection [3], and the cells involved in innate and adaptive responses are often
overlapped implying the concomitant activation of the downstream immune activation [2]. Considering all these phenomena of bodily immune responses to therapeutic radioisotope-labeled PEGylated nanomaterials, what we need to get is how
much of the injected materials are reaching the targets while other innate or
adaptive immune organs are responding to the collateral accumulation of the same
therapeutic materials. Further to this, how much amount of radioactivity should be
given to the patients should also be elucidated using the preclinical PET/SPECT
imaging and individualized dosimetry. Understanding the fate of radionanomedicines made of radiolabeled nanomaterials in human will be feasible
referring all the facts and principles of innate immunity as well as adaptive
immunity and physiology unique to the human being.
References
1. L.L. Lanier, Shades of grey–the blurring view of innate and adaptive immunity. Nat. Rev.
Immunol. 13(2), 73–74 (2013)
2. E. Vivier, D.H. Raulet, A. Moretta, M.A. Caligiuri, L. Zitvogel, L.L. Lanier et al., Innate or
adaptive immunity? The example of natural killer cells. Science 331(6013), 44–49 (2011)
3. M.G. Netea, L.A. Joosten, E. Latz, K.H. Mills, G. Natoli, H.G. Stunnenberg et al., Trained
immunity: a program of innate immune memory in health and disease. Science 352(6284),
aaf1098 (2016)
4. A. Doni, C. Garlanda, A. Mantovani, Innate immunity, hemostasis and matrix remodeling:
PTX3 as a link. Semin. Immunol. 28(6), 570–577 (2016)
5. X. Cao, Self-regulation and cross-regulation of pattern-recognition receptor signalling in
health and disease. Nat. Rev. Immunol. 16(1), 35–50 (2016)
6. S.Y. Seong, P. Matzinger, Hydrophobicity: an ancient damage-associated molecular pattern
that initiates innate immune responses. Nat. Rev. Immunol. 4(6), 469–478 (2004)
7. D. Gao, W. Li, Structures and recognition modes of toll-like receptors. Proteins 85(1), 3–9
(2017)
8. N. Nakamoto, T. Kanai, Role of toll-like receptors in immune activation and tolerance in the
liver. Front. Immunol. 5, 221 (2014)
9. J.D. Jones, R.E. Vance, J.L. Dangl, Intracellular innate immune surveillance devices in plants
and animals. Science 354(6316), 1117 (2016)
10. J. Zhu, W.E. Paul, CD4 T cells: fates, functions, and faults. Blood 112(5), 1557–1569 (2008)
404
D. S. Lee and Y. K. Shin