DÄ internationalArchive31-32/2009The Treatment of Colorectal Carcinoma With Monoclonal Antibodies: Subsequent Immunological Mechanisms

Correspondence

The Treatment of Colorectal Carcinoma With Monoclonal Antibodies: Subsequent Immunological Mechanisms

Dtsch Arztebl Int 2009; 106(31-32): 526. DOI: 10.3238/arztebl.2009.0526a

Tsamaloukas, A G

LNSLNS The effectiveness of monoclonal antibodies in oncology and hematology depends—in addition to their effect on the "target"—on whether subsequent immunological mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) are triggered. It is regarded as confirmed that ADCC and CDC depend on sufficient glycosylation of the antibodies. The extent of ADCC is determined by the FcgRIII (CD64) polymorphism and the FcgRIII (CD16a) polymorphism of the Fc moiety of the IgG1 isotype of the monoclonal antibodies. This mechanism has been shown for rituximab in the treatment of follicular lymphoma (1), for trastuzumab in metastatic breast cancer (2), and for cetuximab in the treatment of metastatic colorectal cancer (3). Panitumumab as a human monoclonal antibody of the IgG2 isotype does not trigger ADCC but may trigger CDC and, if administered sequentially, the formation of anti-idiotypic antibodies. The two other EGFR directed antibodies that need mentioning are matuzumab and nimotuzumab. Nimotuzumab is of particularly interest because in the treatment of pediatric malignant gliomas and in non-small cell bronchial carcinoma it did not show any symptoms of the known cutaneous toxicity, especially not acneiform exanthema. This antibody has been licensed in several European countries and is currently being tested in phase III trials for further indications.
DOI: 10.3238/arztebl.2009.0526a


Dr. med. A. G. Tsamaloukas
Schulstr. 16–18, 40721 Hilden, Germany
tsamaloukas@onkologe-hilden.de
1.
Weng WK, Levy R: Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 2003; 21: 3940–7. MEDLINE
2.
Musolino A et al.: Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008; 26: 1789–96. MEDLINE
3.
Bibeau F et al.: Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 2009; 27: 1122–9. MEDLINE
4.
Stintzing S, Heinemann V, Jung A, Moosmann N, Hiddemann W, Kirchner T: The treatment of colorectal carcinoma with monoclonal antibodies—the importance of KRAS mutation analysis and EGFR status [Behandlung des kolorektalen Karzinoms mit monoklonalen Antikörpern – Bedeutung der KRAS Mutationsanalyse und des EGFR-Status]. Dtsch Arztebl Int 2009; 106: 202–6. VOLLTEXT
1. Weng WK, Levy R: Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 2003; 21: 3940–7. MEDLINE
2. Musolino A et al.: Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 2008; 26: 1789–96. MEDLINE
3. Bibeau F et al.: Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 2009; 27: 1122–9. MEDLINE
4. Stintzing S, Heinemann V, Jung A, Moosmann N, Hiddemann W, Kirchner T: The treatment of colorectal carcinoma with monoclonal antibodies—the importance of KRAS mutation analysis and EGFR status [Behandlung des kolorektalen Karzinoms mit monoklonalen Antikörpern – Bedeutung der KRAS Mutationsanalyse und des EGFR-Status]. Dtsch Arztebl Int 2009; 106: 202–6. VOLLTEXT