      Document 0101
 DOCN  DRG0101
 UNIQUE IDENTIFIER        DRG-0146
 NAME OF SUBSTANCE        Lymphocytes, Activated [NIAID 92 I-248]
 SYNONYMS                 Activated lymphocytes [NIAID 92 I-248]
 SYNONYMS                 Autologous CD8+ T lymphocytes [Blood 1993 Apr
                          15;81(8)]
 PROTOCOL ID NUMBERS      NIAID 92 I-248
 PROTOCOL ID NUMBERS      NIAID DATRI 006
 PROTOCOL ID NUMBERS      NIAID 94 I-206
 PROTOCOL ID NUMBERS      NIAID 93 I-110
 PROTOCOL ID NUMBERS      NIAID 96 HG-51
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   Type of adoptive immunotherapy. Peripheral
                          blood lymphocytes are obtained from a donor
                          by leukapheresis. T lymphocytes are then
                          induced to polyclonal proliferation with
                          anti-CD3 and rIL-2 stimulation. After
                          expansion in culture, the activated
                          lymphocytes are infused into an
                          HIV-seropositive recipient. Pharmacokinetic
                          data has been collected on subjects who were
                          infused with 0.8 x 10--9 to 10 x 10--9 cells
                          including less than or equal to 10--9 cells
                          labelled with 111 indium. In three subjects
                          the infusion was repeated and IL-2, 10--6
                          units/day for 5 days, was given by continuous
                          infusion. In the vascular compartment, the
                          initial (distribution) t1/2 was approximately
                          10 minutes but after 60-90 minutes, clearance
                          remained stable and slow for up to 120 hours.
                          The t1/2 (elimination) was 16.5 hours
                          (mean,N-3) when IL-2 was given and 32.6 hours
                          without IL-2 (N=4). The label appeared
                          rapidly in the lungs, reaching a maximum of
                          67% (N=4) of the body burden in four hours.
                          Significant amounts (7-14%) were also seen in
                          the liver, spleen, and bone marrow at this
                          time. Over the next 60-72 hours, the label
                          shifted from the lungs to the other organs
                          stabilizing at about 72 hours, with 46.3%,
                          23.3%, 20% and 27.5% in the bone marrow,
                          liver, spleen and lungs, respectively. The
                          distribution was not significantly affected
                          by IL-2 infusion. Over 96 hours, about 10% of
                          the label appeared in the urine. The lifespan
                          of these cells remains unclear, but maximally
                          90% remain intact for 5 days. [Blood 1993 Apr
                          15;81(8)] [Int Conf AIDS 1992 Jul
                          19-24;8(2):(abstract no. PoB 3452)]
 DISEASES STUDIED/TREATED Enhancement of immune function in HIV
                          infection [Blood 1993 Apr 15;81(8)]
 CLASSIFICATION CODE      Immunomodulator [Blood 1993 Apr 15;81(8)]
 ADVERSE EFFECTS          Adverse effects may include chills, fever,
                          tachycardia, nausea, vomiting, shortness of
                          breath, muscle aches, joint aches, local pain
                          and redness at site of infusion, skin rash,
                          and severe allergic reaction. [NIAID 92
                          I-248]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: CD8+ T lymphocytes [Blood
                          1993 Apr 15;81(8)]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous infusion.
                          [Blood 1993 Apr 15;81(8)]
 MANUFACTURERS            National Institute of Allergy & Infectious
                          Diseases
 MANUFACTURERS            Tufts University
 REFERENCES               Lieberman J, Fabry JA, Skolnik PR, Parkerson
                          GR, Fong DM, Kagan J, Standiford H, Lee E,
                          Landry B. Immunotherapy with autologous
                          HIV-specific CTL. Int Conf AIDS. 1994 Aug
                          7-12;10(1):220 (abstract no. PBO311)
 REFERENCES               Whiteside TL, Elder EM, Moody D, Armstrong J,
                          Ho M, Rinaldo C, Huang X, Torpey D, Gupta P,
                          McMahon D, et al. Generation and
                          characterization of ex vivo propagated
                          autologous CD8+ cells used for adoptive
                          immunotherapy of patients infected with human
                          immunodeficiency virus. Blood 1993 Apr
                          15;81(8):2085-92.
 REFERENCES               Ho M, Armstrong J, McMahon D, Pazin G, Huang
                          XL, Rinaldo C, Whiteside T, Tripoli C, Levine
                          G, Moody D, et al. A phase I study of
                          adoptive transfer of autologous CD8+ T
                          lymphocytes in patients with acquired
                          immunodeficiency syndrome (AIDS)-related
                          complex or AIDS. Blood 1993 Apr
                          15;81(8):2093-101.
 REFERENCES               Moody DJ, Kremer AM, Kahn J, Okarma TB.
                          Impact of CD8+ cellular therapy with
                          concomitant IL-2 administration on the
                          peripheral blood lymphocyte composition in
                          AIDS patients with Kaposi's sarcoma. Int Conf
                          AIDS. 1993 Jun 6-11;9(1):495 (abstract no.
                          PO-B28-2162).
 REFERENCES               Torpey D 3d, Huang XL, Armstrong J, Ho M,
                          Whiteside T, McMahon D, Pazin G, Heberman R,
                          Gupta P, Tripoli C, et al. Effects of
                          adoptive immunotherapy with autologous CD8+ T
                          lymphocytes on immunologic parameters:
                          lymphocyte subsets and cytotoxic activity.
                          Clin Immunol Immunopathol. 1993
                          Sep;68(3):263-72.
 REFERENCES               Tauxe N, Ho M, Levine J, McMahon D, Elder E,
                          Whiteside T, Moody D, Okarma T, Armstrong J,
                          Herberman R. Distribution and trafficking of
                          autologous, expanded CD8+ cells infused in
                          subjects with AIDS or ARC. Int Conf AIDS 1992
                          Jul 19-24;8(2):B162 (abstract no. PoB 3452).
 REFERENCES               Whiteside T, Elder E, Armstrong J, Moody DJ,
                          Okarma TB, Herberman RB, Ho M.
                          Characteristics of ex vivo propagated
                          autologous CD8+ T-cells used in the treatment
                          of patients infected with human
                          immunodeficiency virus. Int Conf AIDS. 1992
                          Jul 19-24;8(2):A35 (abstract no. PoA 2195).
 REFERENCES               Armstrong JA, Ho M, Herberman R, Elder E,
                          Ferbas J, McMahon D, Gupta P, Rinaldo C,
                          Whiteside T. A phase I study of autologous,
                          activated CD8(+) lymphocytes expanded in
                          vitro infused into patients with advanced ARC
                          or AIDS (ACTG 080). Int Conf AIDS. 1990 Jun
                          20-23;6(3):208 (abstract no. S.B.491).
 ENTRY MONTH              9209
 LAST REVISION DATE       960612
 

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