      Document 0055
 DOCN  DRG0055
 UNIQUE IDENTIFIER        DRG-0192
 NAME OF SUBSTANCE        F105 human monoclonal antibody [NIAID ACTG
                          232]
 SYNONYMS                 F105 [J Acquir Immune Defic Syndr 1993
                          Jan;6(1)]
 SYNONYMS                 F105 mAb [J Clin Invest 1992 Oct;90(4)]
 SYNONYMS                 mAb F105 [J Clin Invest 1992 Oct;90(4)]
 SYNONYMS                 Human mAb [J Immunol 1991 Jun 15;146(12)]
 SYNONYMS                 HmAb [J Immunol 1991 Jun 15;146(12)]
 SYNONYMS                 Monoclonal antibody F105 [J Clin Invest 1995
                          Feb;95(2)]
 PROTOCOL ID NUMBERS      NIAID ACTG 232
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The antibody reacts with the
                          CD4 binding region of GP120. F105 neutralizes
                          the IIIB, SF2 and MN strains of HIV at
                          concentrations readily achievable in man
                          (1.50 - 10 mcg/ml). The F105 antibody does
                          not neutralize some strains of virus at
                          fairly high doses in vitro assays.
                          Nonetheless, F105 does react with GP120 from
                          these non-neutralized strains and also
                          promotes cellular immunity in the form of
                          antibody dependent cellular cytotoxicity
                          against diverse viral strains. The F105
                          epitope on GP120 is a conformational epitope
                          and overlaps significantly the CD4 binding
                          region on GP120. Other CD4 binding site Hmab
                          overlap with F105 and have similar
                          neutralization profiles. F105 offers a
                          potential alternative to RCD4-IgG as a
                          biological treatment for HIV infection
                          because it reacts with an immunogenic epitope
                          on GP120 and avoids the problems related to
                          the possible normal functions of CD4 within
                          the immune system, and lacks the potential
                          immunogenicity and instability of the
                          nonbinding structures of the CD4 portion of
                          the artificial construct. The disposition of
                          F105 has not been studied in humans. However,
                          data in cynomolgus monkeys has shown the
                          terminal half-life of mean F105
                          concentrations to be 9.6 days. [NIAID ACTG
                          232] [J Immunol 1991 Jun 15;146(12)] [J Clin
                          Invest 1995 Feb;95(2)]
 DISEASES STUDIED/TREATED Inhibition of tumor necrosis factor
                          production in HIV infection [NIAID ACTG 232]
 CLASSIFICATION CODE      Immunomodulator [NIAID ACTG 232]
 ADVERSE EFFECTS          Adverse effects include mild headache and
                          backache. [AIDS Therapies 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: This human monoclonal
                          antibody, F105, is an IgG1 kappa antibody
                          produced by a hybridoma constructed from an
                          EBV transformant fused with a human myeloma
                          analogue [NIAID ACTG 232]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Single use 10 ml glass vials
                          containing 5.0 mg/ml of F105. [NIAID ACTG
                          232]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous. [NIAID ACTG
                          232]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Should be stored at 2-8
                          C. [NIAID ACTG 232]
 MANUFACTURERS            Centocor Incorporated
 REFERENCES               Cavacini LA, Emes CL, Power J, Desharnais FD,
                          Duval M, Montefiori D, Posner MR. Influence
                          of heavy chain constant regions on antigen
                          binding and HIV-1 neutralization by a human
                          monoclonal antibody. J Immunol. 1995 Oct
                          1;155(7):3638-44.
 REFERENCES               Khouri YF, McIntosh K, Cavacini L, Posner M,
                          Pagano M, Tuomala R, Marasco WA. Vertical
                          transmission of HIV-1. Correlation with
                          maternal viral load and plasma levels of CD4
                          binding site anti-gp120 antibodies. J Clin
                          Invest. 1995 Feb;95(2):732-7.
 REFERENCES               Burton DR, Pyati J, Koduri R, Sharp SJ,
                          Thornton GB, Parren PW, Sawyer LS, Hendry RM,
                          Dunlop N, Nara PL, et al. Efficient
                          neutralization of primary isolates of HIV-1
                          by a recombinant human monoclonal antibody.
                          Science. 1994 Nov 11;266(5187):1024-7.
 REFERENCES               Cavacini LA, Power J, Emes CL, Mace K, Treacy
                          G, Posner MR. Plasma pharmacokinetics and
                          biological activity of a human
                          immunodeficiency virus type 1 neutralizing
                          human monoclonal antibody, F105, in
                          cynomolgus monkeys. J Immunother Emphasis
                          Tumor Immunol. 1994 May;15(4):251-6.
 REFERENCES               Cavacini LA, Emes CL, Power J, Duval M,
                          Posner MR. Effect of antibody valency on
                          interaction with cell-surface expressed HIV-1
                          and viral neutralization. J Immunol. 1994 Mar
                          1;152(5):2538-45.
 REFERENCES               Cavacini LA, Emes CL, Power J, Underdahl J,
                          Goldstein R, Mayer K, Posner MR. Loss of
                          serum antibodies to a conformational epitope
                          of HIV-1/gp120 identified by a human
                          monoclonal antibody is associated with
                          disease progression. J Acquir Immune Defic
                          Syndrome. 1993 Oct;6(10):1093-102.
 REFERENCES               Posner MR, Cavacini LA, Emes CL, Power J,
                          Byrn R. Neutralization of HIV-1 by F105, a
                          human monoclonal antibody to the CD4 binding
                          site of gp120. J Acquir Immune Defic Syndr.
                          1993 Jan;6(1):7-14.
 ENTRY MONTH              9401
 LAST REVISION DATE       960417
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
