Chimeric mAb vs Humanized mAb
[Figure] Sketches of chimeric (top right), humanized (bottom left) and chimeric/humanized (bottom middle) monoclonal antibodies. Human parts are shown in brown, non-human parts in blue.
(-o-:mouse, -u-:human, -xi-:chimeric, -zu-:humanized, -xizu-:humanized chimeric)
(출처: http://en.wikipedia.org/wiki/Humanized_antibody)
Cetuximab (trade name Erbitux)
is an epidermal growth factor receptor (EGFR) inhibitor used for the treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal antibody given by intravenous infusion that is distributed under the trade name Erbitux in the U.S. and Canada by the drug company Bristol-Myers Squibb and outside the U.S. and Canada by the drug company Merck KGaA. In Japan, Merck KGaA, Bristol-Myers Squibb and Eli Lilly have a co-distribution.
(출처: http://en.wikipedia.org/wiki/Cetuximab)
[2013년 기준 글로벌 판매액]
Rituximab (trade names Rituxan, MabThera and Zytux)
is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. Rituximab destroys B cells and is therefore used to treat diseases which are characterized by excessive numbers of B cells, overactive B cells, or dysfunctional B cells. This includes many lymphomas, leukemias, transplant rejection, and autoimmune disorders.
(출처: http://en.wikipedia.org/wiki/Rituximab)
Trastuzumab (trade names Herclon, Herceptin)
is a monoclonal antibody that interferes with the HER2/neu receptor. Its main use is to treat certain breast cancers.
The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules called EGFs) to inside the cell, and turn genes on and off. The HER proteins stimulate cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably.
The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) breast cancer from 20.3 to 25.1 months. In early stage breast cancer, it reduces the risk of cancer returning after surgery by an absolute risk of 9.5%, and the risk of death by an absolute risk of 3% however increases serious heart problems by an absolute risk of 2.1% which may resolve if treatment is stopped.
Trastuzumab is also being studied for the treatment of other cancers. It has been used with some success in women with uterine papillary serous carcinomas that overexpress HER2/neu.
Medical use
The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months. In early stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery by an absolute risk of 9.5%, and the risk of death by an absolute risk of 3%; however, it increases serious heart problems by an absolute risk of 2.1%, though the problems may resolve if treatment is stopped.
Trastuzumab has had a "major impact in the treatment of HER2-positive metastatic breast cancer". The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone.
| Type | Whole antibody |
|---|---|
| Source | Humanized (from mouse) |
| Target | HER2/neu |
(출처: http://en.wikipedia.org/wiki/Trastuzumab)
Bevacizumab (pronounced /bev-a-Sizz-uh-mab/, trade name Avastin, Genentech/Roche)
is an angiogenesis inhibitor, as a drug that slows the growth of new blood vessels.
Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A). VEGF-A is a chemical signal that stimulates angiogenesis in a variety of diseases, especially in cancer. Bevacizumab was the first clinically available angiogenesis inhibitor in the United States.[citation needed]
Bevacizumab was approved by the U.S. Food and Drug Administration (FDA) for certain metastatic cancers. It received its first approval in 2004, for combination use with standard chemotherapy for metastatic colon cancer. It has since been approved for use in certain lung cancers, renal cancers, ovarian cancers, and glioblastoma multiforme of the brain. It had been approved for breast cancer, but that approval was withdrawn when later studies showed no evidence of effectiveness.
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Target | VEGF-A |
(출처: http://en.wikipedia.org/wiki/Bevacizumab)
Erlotinib (Erlotinib hydrochloride, trade name Tarceva)
is a drug used to treat non-small cell lung cancer (NSCLC), pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). It is marketed in the United States by Genentech and OSI Pharmaceuticals and elsewhere by Roche.
Erlotinib is an EGFR inhibitor. The drug follows Iressa (gefitinib), which was the first drug of this type. Erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. For the signal to be transmitted, two EGFR molecules need to come together to form a homodimer. These then use the molecule of ATP to trans-phosphorylate each other on tyrosine residues, which generates phosphotyrosine residues, recruiting the phosphotyrosine-binding proteins to EGFR to assemble protein complexes that transduce signal cascades to the nucleus or activate other cellular biochemical processes. By inhibiting the ATP, formation of phosphotyrosine residues in EGFR is not possible and the signal cascades are not initiated.
(출처: http://en.wikipedia.org/wiki/Erlotinib)
Crizotinib (trade name Xalkori, Pfizer),
is an anti-cancer drug acting as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor, approved for treatment of some non-small cell lung carcinoma (NSCLC) in the US and some other countries, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.
Crizotinib has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosomal rearrangement that generates a fusion gene between EML4 ('echinoderm microtubule-associated protein-like 4') and ALK ('anaplastic lymphoma kinase'), which results in constitutive kinase activity that contributes to carcinogenesis and seems to drive the malignant phenotyp The kinase activity of the fusion protein is inhibited by crizotinib. Patients with this gene fusion are typically younger non-smokers who do not have mutations in either the epidermal growth factor receptor gene (EGFR) or in the K-Ras gene. The number of new cases of ALK-fusion NSLC is about 9,000 per year in the U.S. and about 45,000 worldwide. ALK mutations are thought to be important in driving the malignant phenotype in about 15% of cases of neuroblastoma, a rare form of peripheral nervous system cancer that occurs almost exclusively in very young children. Crizotinib inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms.
Crizotinib is currently thought to exert its effects through modulation of the growth, migration, and invasion of malignant cells. Other studies suggest that crizotinib might also act via inhibition of angiogenesis in malignant tumors.
(출처: http://en.wikipedia.org/wiki/Crizotinib)
Pemetrexed (brand name Alimta)
is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma and non-small cell lung cancer.
Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.
(출처: http://en.wikipedia.org/wiki/Pemetrexed)
