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New perspectives on complement mediated immunotherapy

Stasiłojć, Grzegorz; Österborg, Anders; Blom, Anna M. LU and Okrój, Marcin LU (2016) In Cancer Treatment Reviews 45. p.68-75
Abstract

Tumor-specific monoclonal antibodies (mAbs) offer several modes of tumor cell killing, from direct cytotoxic activity to indirect mechanisms employing the host immune system, particularly its innate branch. The latter effector functions seem to dominate among clinically approved anti-cancer mAbs and major efforts are being undertaken by both academia and the pharmaceutical industry with the aim to improve complement activation, antibody-dependent cellular cytotoxicity (ADCC) and Fc/opsonin-mediated phagocytosis. On one hand, there are a variety of available effector mechanisms to allow multistep elimination of tumor cells. On the other hand, tumor cells adopt a number of strategies to evade immune attack, such as overexpression of... (More)

Tumor-specific monoclonal antibodies (mAbs) offer several modes of tumor cell killing, from direct cytotoxic activity to indirect mechanisms employing the host immune system, particularly its innate branch. The latter effector functions seem to dominate among clinically approved anti-cancer mAbs and major efforts are being undertaken by both academia and the pharmaceutical industry with the aim to improve complement activation, antibody-dependent cellular cytotoxicity (ADCC) and Fc/opsonin-mediated phagocytosis. On one hand, there are a variety of available effector mechanisms to allow multistep elimination of tumor cells. On the other hand, tumor cells adopt a number of strategies to evade immune attack, such as overexpression of complement inhibitors, trogocytosis, shedding or internalization of mAb-targeted epitopes, which all contribute to their resistance against host defense mechanisms. Another problem recognized only recently is the depletion of immune effectors during the first round of treatment, which in concordance with delayed turnover of immune components renders subsequent rounds of therapy ineffective. Herein, we discuss newly identified limiting factors but also novel mechanistic data on complement activation by antitumor antibodies as issues important for guidance towards the next generations of immunotherapeutics.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CD20, Complement system, Immunotherapy
in
Cancer Treatment Reviews
volume
45
pages
8 pages
publisher
WB Saunders
external identifiers
  • Scopus:84960887950
  • WOS:000374611500008
ISSN
0305-7372
DOI
10.1016/j.ctrv.2016.02.009
language
English
LU publication?
yes
id
177b8245-c492-4fea-a6a4-dd80934de88b
date added to LUP
2016-05-13 16:34:15
date last changed
2016-11-13 04:39:33
@misc{177b8245-c492-4fea-a6a4-dd80934de88b,
  abstract     = {<p>Tumor-specific monoclonal antibodies (mAbs) offer several modes of tumor cell killing, from direct cytotoxic activity to indirect mechanisms employing the host immune system, particularly its innate branch. The latter effector functions seem to dominate among clinically approved anti-cancer mAbs and major efforts are being undertaken by both academia and the pharmaceutical industry with the aim to improve complement activation, antibody-dependent cellular cytotoxicity (ADCC) and Fc/opsonin-mediated phagocytosis. On one hand, there are a variety of available effector mechanisms to allow multistep elimination of tumor cells. On the other hand, tumor cells adopt a number of strategies to evade immune attack, such as overexpression of complement inhibitors, trogocytosis, shedding or internalization of mAb-targeted epitopes, which all contribute to their resistance against host defense mechanisms. Another problem recognized only recently is the depletion of immune effectors during the first round of treatment, which in concordance with delayed turnover of immune components renders subsequent rounds of therapy ineffective. Herein, we discuss newly identified limiting factors but also novel mechanistic data on complement activation by antitumor antibodies as issues important for guidance towards the next generations of immunotherapeutics.</p>},
  author       = {Stasiłojć, Grzegorz and Österborg, Anders and Blom, Anna M. and Okrój, Marcin},
  issn         = {0305-7372},
  keyword      = {CD20,Complement system,Immunotherapy},
  language     = {eng},
  month        = {04},
  pages        = {68--75},
  publisher    = {ARRAY(0xad03688)},
  series       = {Cancer Treatment Reviews},
  title        = {New perspectives on complement mediated immunotherapy},
  url          = {http://dx.doi.org/10.1016/j.ctrv.2016.02.009},
  volume       = {45},
  year         = {2016},
}