IV - Transplantation and Immunology - 24 25

• I. Specific T cell inhibitors - Cyclosporine, Tacrolimus
• II. Cytotoxic drugs - Azathioprine, Cyclophosphamide, Methotrexate, Chlorambucil
• III. Glucocorticoids - Prednisolone
• IV. Antibiotics - Muromonab CD3, Antithymocyte globulin (ATG), Rhe immunoglobulin

Leflunomide is an immunosuppressive drug capable of inhibiting T and B cell response in vivo.

• o Cyclosporine is a calcineurin inhibitor; binds cyclophilin.
• o Blocks T cell activation  by preventing IL-2 transcription.

• Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones.
• Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer.

Approximately 20 different RTK classes have been identified.

• RTK class I (epidermal growth factor receptor (EGFR) family) (ErbB family)
• RTK class II (Insulin receptor family)
• RTK class III (Platelet-derived growth factor receptors (PDGF-R) family)
• RTK class IV (Vascular endothelial growth factor (VEGF) receptors family)
• RTK class XIV (RET receptor family)

The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR)

• The ErbB protein family consists of 4 members
• ErbB-1, also named epidermal growth factor receptor (EGFR)
• ErbB-2, also named HER2 in humans and neu in rodents
• ErbB-3, also named HER3
• ErbB-4, also named HER4

EGFR inhibitors - 

ErbB-1 inhibitor - panitumumab, cetuximab, gefitinib, erlotinib, afatinib

HER-2 receptor blocker - trastuzumab


Imatinib works by stopping the Bcr-Abl tyrosine-kinase.

• Cetuximab is a chimeric (mouse-human) monoclonal antibody; panitumumab, a fully human monoclonal antibody, binds to and inhibits the EGFR, which is overexpressed in 60% to 80% of colorectal cancers and is associated with a shorter survival time.
• Cetuximab and panitumumab are effective only on tumors that do not have a mutation of the KRAS gene.
• Accordingly, genetic testing is now recommended to confirm the absence of KRAS mutations (indicating the presence of the KRAS wild-type gene) before the use of these EGFR inhibitors is recommended.

Platelet-derived growth factor (PDGF) is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation (angiogenesis), the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled angiogenesis is a characteristic of cancer

Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis.

VEGF inhibitors - aflibercept, bevacizumab, and ranibizumab

Small Molecule // Target //  Disease

Imatinib (Gleevec) //  PDGFR, KIT, Abl, Arg // SML, GIST

Gefitinib (Iressa) // EGFR // Esophageal cancer, Glioma

Erlotinib (Tarceva) //  EGFR // Esophageal cancer, Glioma

Sorafenib (Nexavar) // Raf, VEGFR, PDGFR, Flt3, KIT // Renal cell carcinoma

Sunitinib (Sutent) // KIT, VEGFR, PDGFR, Flt3 // Renal cell carcinoma, GIST, Endocrine pancreatic cancer

Desatinib (Sprycel) //  Abl, Arg, KIT, PDGFR, Src // Gleevec-resistant CML

Nilotinib (Tasigna) // Abl, Arg, KIT, PDGFR // Gleevec-resistant CML

Lapatinib (Tykerb) //  EGFR, ErbB2 // Mammary carcinoma

Trastuzumab (Herceptin) //  ErbB2 // Mammary carcinoma

Cetuximab (Erbitux) // EGFR // Colorectal cancer, Head and neck cancer

Bevacizumab (Avastin) // VEGF // Lung cancer, Colorectal cancer

Panitumumab (Vectibix) // EGFR // Colorectal cancer

EGFR blockers are effective only on the tumors that do not have a mutation of K-ras gene. Genetic testing is now recommended to confirm the absence of K-ras mutation (indicating the presence of K-ras wild type gene) before the use of EGFR inhibitors.