Nimotuzumab (h-R3mAb, TheraCIM) is an EGFR targeting monoclonal antibody approved for glioma, malignant astrocytomes and squamous cell carcinoma of head and neck in several countries outside US. Phase II/III studies for FDA approval are ongoing.
Like cetuximab (Erbitux) and panitumumab (Vectibix), nimotuzumab targets EGFR. Transtuzumab is specific for HER2/neu. However, unlike cetuximab and panitumumab, nimotuzumab does not appear to have side effects of rashes and hypomagnesemia.
Side-Effect
|
Nimotuzumab
plus radiationa |
Erbitux®
plus radiationb |
Vectibix®
plus BSCb,c |
BSC
Aloneb |
Rash/Skin Reactions - grades 3 and 4
|
<1%
|
25%d
|
62%e
|
0%
|
Rash/Skin Reactions - all grades
|
9%
|
87%
|
90%
|
6%
|
Pruritus
|
<1%
|
16%
|
57%
|
2%
|
Hypomagnesemia - all grades
|
<1%
|
50%
|
39%
|
2%
|
Nausea
|
22%
|
49%
|
23%
|
16%
|
Diarrhea
|
9%
|
19%
|
21%
|
11%
|
Constipation
|
14%
|
35%
|
21%
|
9%
|
Vomiting
|
14%
|
29%
|
19%
|
12%
|
(Source: YM Biosciences)
One reason explained in company's slideshare presentation is that nimotuzumab (just like transtuzumab) requires high density receptors to bind. This preferentially targets MAB to high EGFR-expressing tumors. (Read here) A comparative in vitro study comparing EGF receptor binding, signal transduction and ADCC activity of cetuximab, panitumumab, and nimotuzumab was presented by EMD Serono at the recent ASCO 2010 meeting. In cellular assays, nimotuzumab had lower affinity for EGFR, showed less inhibition of EGFR signal transduction (phospho-EGFR, phospho-ERK1/2, phospho-Akt, phospho- STAT3) or VEGF and IL-8 production, and displayed weak ADCC activity. The EMD Serono team concluded that different modes of action underlie clinical efficacy outcomes and toxicity profiles (Read here)
Further Readings:
- The Epidermal Growth Factor Receptor Pathway: A Model for Targeted Therapy. Scaltriti M, Baselga J. Clinical Cancer Research Sept 2006 12; 5268 | DOI |
- SnapShot: EGFR signaling pathway. Yarden Y, Shilo BZ. Cell. 2007 Nov 30;131(5):1018. | PubMed | FreePDF |
- Pharmacological and immunological characteristics of the therapeutic anti-EGFR antibodies cetuximab, panitumumab, and nimotuzumab. C. Stroh, et al. J Clin Oncol 28, 2010 (suppl; abstr e13025)
Drugs:
Cetuximab (IMC-C225, Erbitux) is a chimeric mouse/human antibody [Wikipedia] Nimotuzumab sold as BIOMAb EGFR (Biocon) in India, as Theracim (YM Biosciences) in Cuba, as Theraloc (Oncosciences) in Europe, is a humanized antibody [Wikipedia]
Panitumumab (ABX-EGF, Vectibix Amgen) is human antibody [Wikipedia]
Trastuzumab (Herceptin) is humanized antibody - targets HER2/neu [Wikipedia]
Related Posts:
Understanding resistance to targeted cancer therapies via systems biology (Nov 08, 2010)
Random Finds: A Roadmap of Cancer Systems Biology by Edwin Wang (Nov 02, 2010)
Random Finds: A Roadmap of Cancer Systems Biology by Edwin Wang (Nov 02, 2010)
No comments:
Post a Comment