Inhibition of hematopoietic progenitor colony growth by a monoclonal antibody against the transferrin receptor: Comparison of unconjugated antibody with an immunotoxin containing recombinant ricin a chain

1990 ◽  
Vol 8 (5) ◽  
pp. 368-376
Author(s):  
Kevin M. Shannon ◽  
David B. Ring ◽  
L. Houston ◽  
Vann Schaffner ◽  
Juliette Naylor ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Transferrin Receptor ◽  
Colony Growth ◽  
Hematopoietic Progenitor ◽  
Ricin A Chain ◽  
A Chain ◽  
Ricin A

scholarly journals Amantadine potentiates T lymphocyte killing by an anti-pan-T cell (CD5) ricin A-chain immunotoxin

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 345-348 ◽  
Author(s):  
S Siena ◽  
S Villa ◽  
M Bregni ◽  
G Bonnadonna ◽  
AM Gianni
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocyte ◽  
Ex Vivo ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Ricin A Chain ◽  
Human Therapy ◽  
A Chain ◽  
Ricin A

Abstract The studies described in this report demonstrate that 1-adamantanamine hydrochloride (amantadine) is a potent enhancer of the cytotoxic activity of the anti-pan-T lymphocyte (CD5) T101 monoclonal antibody conjugated to purified ricin A-chain (T101-immunotoxin; T101-IT). We also demonstrate that T101-IT in the presence of amantadine does not induce immunotoxin-mediated cytotoxicity in nontarget cells such as human marrow hematopoietic progenitor cells. These results provide further knowledge for the improvement of ex vivo purification of human bone marrow from normal or leukemic T cells prior to allogeneic or autologous stem cell transplantation, respectively. Furthermore, since amantadine has long been employed safely in human therapy, its use in conjunction with immunotoxins might be exploited in vivo.

scholarly journals Amantadine potentiates T lymphocyte killing by an anti-pan-T cell (CD5) ricin A-chain immunotoxin

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 345-348
Author(s):  
S Siena ◽  
S Villa ◽  
M Bregni ◽  
G Bonnadonna ◽  
AM Gianni
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocyte ◽  
Ex Vivo ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Ricin A Chain ◽  
Human Therapy ◽  
A Chain ◽  
Ricin A

The studies described in this report demonstrate that 1-adamantanamine hydrochloride (amantadine) is a potent enhancer of the cytotoxic activity of the anti-pan-T lymphocyte (CD5) T101 monoclonal antibody conjugated to purified ricin A-chain (T101-immunotoxin; T101-IT). We also demonstrate that T101-IT in the presence of amantadine does not induce immunotoxin-mediated cytotoxicity in nontarget cells such as human marrow hematopoietic progenitor cells. These results provide further knowledge for the improvement of ex vivo purification of human bone marrow from normal or leukemic T cells prior to allogeneic or autologous stem cell transplantation, respectively. Furthermore, since amantadine has long been employed safely in human therapy, its use in conjunction with immunotoxins might be exploited in vivo.

scholarly journals Internalization and intracellular fate of anti-CD5 monoclonal antibody and anti-CD5 ricin A-chain immunotoxin in human leukemic T cells

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1511-1517 ◽  
Author(s):  
S Ravel ◽  
M Colombatti ◽  
P Casellas
Keyword(s):  
Monoclonal Antibody ◽  
Direct Evidence ◽  
Intracellular Localization ◽  
Ricin A Chain ◽  
Golgi Compartment ◽  
Internalization Process ◽  
A Chain ◽  
Kinetics Of ◽  
Intracellular Fate ◽  
Ricin A

Abstract We have investigated the entry and subsequent intracellular fate of T101 monoclonal antibody (MoAb) and T101-ricin A-chain (RTA) immunotoxin (IT) directed against the CD5 antigen (Ag) expressed on human leukemic CEM cells. We provide direct evidence for the internalization of T101 MoAb and the corresponding IT. Both the MoAb and IT were internalized at a relatively low rate. This slow internalization process could be related to the partial recycling of the MoAb/Ag or IT/Ag complexes. Analysis of the internalized molecules showed that their molecular weight was only partially altered after internalization and that no free A-chain could be found inside the cells, indicating that lysosomal degradation and cleavage of disulfide- linked conjugates is a quantitatively minor phenomenon compared with the localization of internalized anti-CD5 ITs in an endosomo-Golgi compartment, followed by their recycling to the cell surface. We believe that this is the major factor explaining the low efficacy of anti-CD5 IT when assayed in the absence of potentiating substances. Finally, we showed that the presence of ammonium chloride and monensin, which both dramatically enhance the kinetics of IT activity, did not affect the rate of internalization or the intracellular localization of the conjugate, suggesting that these activators could act at the postendocytotic level on a limited number of IT molecules.

Variants of lymphoid lines produced with ricin A-chain monoclonal antibody conjugates

1985 ◽  
Vol 76 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Jennifer A. Lowe ◽  
N.R. Ling ◽  
J.A. Forrester ◽  
A.J. Cumber ◽  
W.C.J. Ross
Keyword(s):  
Monoclonal Antibody ◽  
Ricin A Chain ◽  
Lymphoid Lines ◽  
Antibody Conjugates ◽  
A Chain ◽  
Ricin A
Sign in / Sign up

Export Citation Format

Share Document