Cancer interleukin-2 treatment

Lotze, M.T. et al., High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer. Responses, treatment-related morbidity, and histologic findings, JAMA, 256, 3117, 1986. 

Several human or recombinant antiproliferative proteins are currently in use for the treatment of cancer. Interleukin-2, interferons, BCG vaccine, tyrosine kinase, epidermal growth factor, proteasome inhibitors, and several monoclonal antibodies directed against tumor cell antigens now augment the cancer chemotherapeutic arsenal. (Readers are directed to Chapter 5 for a more in-depth discussion of the peptides and proteins available for the treatment of neoplastic disease.)... 

NF-kB and COX-2 is a common feature in many cancers, and blocking these proteins usually provides significant chemopreventive potential. Anthocyanins have exhibited anti-inflammatory effects in multiple cell t) es in vitro, through their ability to inhibit the mRNA and/or protein expression levels of COX-2, NF-kB, and various interleukins. Treatment of JB-6 C141 mouse epidermal cells with an anthocyanin-rich extract from black raspberries resulted in the downregulation of benzo(a) pyrene diol-epoxide (BaPDE)-induced NF-kB expression [41]. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Ehtesham M, Kabos P, Kabosova A, Neuman T, Black KL, Yu JS (2002b) The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. Cancer Res 62 5657-5663... 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

Denileukin diftitox is a combination of the active sections of interleukin 2 and diphtheria toxin. It binds to high-affinity interleukin 2 receptors on the cancer cell (and other cells), and the toxin portion of the molecule inhibits protein synthesis to result in cell death. The pharmacokinetics of denileukin diftitox are best described by a two-compartment model, with an a half-life of 2 to 5 minutes and a terminal half-life of 70 to 80 minutes. Denileukin diftitox is used for the treatment of persistent or recurrent cutaneous T-cell lymphoma whose cells express the CD25 receptor. Side effects include vascular leak syndrome, fevers/chills, hypersensitivity reactions, hypotension, anorexia, diarrhea, and nausea and vomiting. 

Fewell JG, Matar MM, Rice JS, Brunhoeber E, Slobodkin G, Pence C, Worker M, Lewis DH, Anwer K (2009) Treatment of disseminated ovarian cancer using nonviral interleukin-12 gene therapy delivered intraperitoneally. J Gene Med 11 718-728... 

Talmadge, J.E. et al., Systematic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease, Cancer Res, 47, 5725, 1987. 

Examples of the early application of recombinant DNA technology in medicine are the development of recombinant human growth hormone human insulin human interferons, thought to have anticancer activity in addition to antiviral activity interleukins (regulatory proteins from lymphocytes that are believed to be important in the treatment of immunodeficiency diseases and cancer) tumor necrosis factor epidermal and bone marrow progenitor cell growth factors and the production of vaccines (Table 12.1). 

Cytokines such as interferons are used for the treatment of hepatitis, cancer, and lymphoma interleukins are used to enhance immune response and growth factors are used for the treatment of anemia and regulation of tumor angiogenesis. 

Also when the cytokine interleukin 2 (IL-2) was used for cancer treatment, serious adverse effects were noted resulting in the so-called vascular leak syndrome (VLS) [98, 99]. VLS is a life-threatening toxicity marked by vasopermeability with hypotension induced during high dose IL-2 treatment of cancer patients [100]. VLS is caused by endothelial activation and can be induced in lungs and liver of mice by IL2 administration [99]. The mechanism of IL-2-induced VLS is still poorly understood and at present there is no specific therapy for VLS. For the investigation of these... 

Aldesleukin is a recombinant form of human Interleukin-2 (IL-2). It has been approved for the treatment of malignant melanoma and renal cell cancer. The medicine is administered every 8 hours by a 15-minute intravenous infusion for a maximum of 14 doses. Adverse reactions include hypo- and hypertension, gastrointestinal disturbances, fever, fatigue, lethargy, joint pain, headache. Cardiovascular problems may occur. 

IL-2 DAB389 (Ontak) Interleukin-2 (IL-2) Binds to IL-2 receptors expressed on cancer cells and T-cell lymphoma DAB389 is a binding-deficient variant of diphtheria toxin Cytotoxicity Approved for treatment of T-cell lymphoma... 

Interleukin-11 is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by... 

Pichert G, Jost LM, Zobeli L, Odermatt B, Pedia G, Stahel RA. Thyroiditis after treatment with interleukin-2 and interferon alpha-2a. Br J Cancer 1990 62(l) 100-4. 

Wang, J., et al. 2001. Gene gun-mediated oral mucosal transfer of interleukin 12 cDNA coupled with an irradiated melanoma vaccine in a hamster model Successful treatment of oral melanoma and distant skin lesion. Cancer Gene Ther 8 705. 

Interleukin-11 is the first growth factor to gain FDA approval for treatment of thrombocytopenia. It is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by patients who experienced severe thrombocytopenia after a previous cycle of chemotherapy. Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia or neutropenia caused by myelosuppressive chemotherapy. Interleukin-11 is given by subcutaneous injection at a dose of 50 g/kg/d. It is started 6-24 hours after completion of chemotherapy and continued for 14-21 days or until the platelet count passes the nadir and rises to > 50,000 cells/ L. 

D.R. Parkinson, C.A. Seipp, J.H. Ein-horn, and D.E. White. 1994. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 271 907-913. 

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