New perspectives on complement mediated immunotherapy
Författare
Summary, in English
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.
Avdelning/ar
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Institutionen för translationell medicin
- Wallenberglaboratoriet, Malmö
Publiceringsår
2016-04-01
Språk
Engelska
Sidor
68-75
Publikation/Tidskrift/Serie
Cancer Treatment Reviews
Volym
45
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Cancer and Oncology
Nyckelord
- CD20
- Complement system
- Immunotherapy
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 0305-7372