Biologic response modifiers

Agents such as the interferons, interleuklin-2, and monoclonal antibodies are classified as biologic re- 

Interleukin-2 (IL-2) is an endogenous cytokine that normally exerts a number of beneficial immunologic responses. In particular, IL-2 stimulates the growth and differentiation of T-cell lymphocytes that are selectively toxic for tumor cells.11,33 Hence, recombinant DNA techniques are now used to synthesize IL-2 so that this agent can be used to treat cancers such as renal cancer and malignant melanoma (see 

Drug(s) Biologic response modifiers Interferons Interferon alfa-2a [Roferon-A] Interferon alfa-2b [Intron-A] Primary Antineoplastic Indication(s) Hairy-cell leukemia Kaposi sarcoma chronic myelocytic leukemia renal and bladder cancers Common Adverse Effects Flulike syndrome [mild fever, chills, malaise] 

Alemtuzumab [Campath] Chronic lymphocytic leukemia Blood disorders [anemia, leukopenia, neutropenia, thrombocytopenia] chest pain, dyspnea infection nausea 

Bevacizumab [Avastin] Colorectal carcinoma Hemorrhage hypertension Gl distress [nausea, vomiting, diarrhea] blood disorders [leukopenia, neutropenia] others 

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R. Renoux and co-workers, in Th. Klein and co-workers. Biological Response Modifiers in Human Oncology and Immunology, Plenum... 

Phthalimides with a-TNF production regulating activity as novel biological response modifiers (a-TNF is a-tumor necrotic factor) 97YZ91. 

Faneti/ole (122) is a biological response modifier with significant immunosuppressant activity It can be synthesized by conversion of 2 phen> lethylamine (120) with ammonium thio cyanate to the corresponding thiourea analogue 121 The synthesis of faneli/ole (122) concludes by thiazole nng formation of 121 by reaction with phenacylbromide Thus its synthesis involves use of the classic Hantzsch procedure in which a bromoacetone analogue and an appropriate thio urea denvative are reacted 143]... 

Agents which enhance the host s response against neoplasias or force them to differentiate are termed biological response modifiers. Examples include interleukin 2 which is used to treat renal cell carcinoma, interferon a which is active against hematologic neoplasias, and tretinoin (all-trans retinoic acid) which is a powerful inducer of differentiation in certain leukemia cells by acting on retinoid receptors. Side effects include influenza like symptoms, changes in blood pressure and edema. 

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. 

J.S. Lazo. Bleomycin. In Cancer Chemotherapy and Biological Response Modifiers Vol 18, H.M. Pinedo, D.L. Longo, B.A. Chabner (Eds). Elsevier New York,... 

Carpentier PA, Duncan DS, Miller SD (2008) GUal toU-hke receptor signaling in central nervous system infection and autoimmunity. Brain Behav Immun 22 140-147 Carr DJ, Serou M (1995) Exogenous and endogenous opioids as biological response modifiers. Immunopharmacology 31 59-71... 

The risk of infection in patients treated with biologic response modifiers must be considered when selecting and monitoring therapy. 

Biologic response modifiers (BRMs) are indicated in patients who have failed an adequate trial of DMARD therapy.1 BRMs may be added to DMARD monotherapy (i.e., methotrexate) or replace ineffective DMARD therapy.22 The decision to select a particular agent generally is based on the prescriber s comfort level with monitoring the safety and efficacy of the medications, the frequency and route of administration, the patient s comfort level or manual dexterity to self-administer subcutaneous injections, the cost, and the availability of insurance coverage.23 In general, BRMs should be avoided in patients with serious infections, demyelinating disorders (e.g., multiple sclerosis or optic neuritis) or heart failure.21... 

Pharmacologic alternatives for psoriasis include topical agents, phototherapy, and systemic agents including the use of biologic response modifiers. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

The most promising types of biologic response modifiers are monoclonal antibodies, cytokines, and fusion proteins.1 Monoclonal antibodies may be chimeric (fused mouse and human segments designated -ximab ), humanized with intermittent murine sequences (designated -zumab ), human backbone with monkey sequences, or fully human.40... 

Therapeutics Recombinant Cytokines and Biological Response Modifiers... 

Natural and Synthetic Biological Response Modifiers (BRMs).159... 

NATURAL AND SYNTHETIC BIOLOGICAL RESPONSE MODIFIERS (BRMs)... 

Talmadge, J.E. and Herberman, R.B., The preclinical screening laboratory Evaluation of immunomodulatory and therapeutic properties of biological response modifiers, Cancer Treat. Rep., 70, 171, 1986. 

Mihich, E., Future perspectives for biological response modifiers A viewpoint, Semin. Oncol., 13, 234, 1986. 

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