A monoclonal antibody to human acute lymphoblastic leukaemia antigen

A ustralia.Summary A series of monoclonal antibodies was produced by immunizing mice with fresh carcinoma of the colon and with the cell line HT-29. These antibodies could be classified into 3 different groups: (a) those which were HT-29 specific and reacted with no other cell line or fresh colon carcinoma samples; (b) antibodies which reacted with HT-29 and were also reactive with a number of other in vitro cell lines; and (c) antibodies which appeared to be specific for carcinoma of the colon cell lines in that they reacted selectively with colon carcinoma cell lines and not with carcinoma lines derived from other tissues. It was clearly shown by immunoperoxidase staining of both normal and neoplastic cells of the gastrointestinal mucosa, from stomach to colon, that these antibodies were not tumour-specific. Indeed, one antibody (250-30.6) has a remarkable specificity for secretory epithelium of any tissue whether it be found in the gastrointestinal tract, respiratory system or urinary system. We question the existence of tumour-specific antigens detected by monoclonal antisera described thus far, and comment on the remarkable specificity of some of the sera produced, emphasized by the secretory cell-specific antibody described herein.

mentioning

confidence: 99%

Monoclonal antibodies to human colon and colorectal carcinoma

Thompson¹,

Jones²,

Pihl³

et al. 1983

“…Antigenic modulation by LI itself, or poor binding to target tumour cells, might also be worth attention. Whatever the reason for the failure of these and other (Houston et al, 1980;Ritz et al, 1980) preliminary attempts at serological therapy, the exploitation of the monoclonal antibody technology in experimental cancer might be furthered by studies with LI. Since L1210 leukaemia has been widely used over the last 30 years and there is good knowledge of its in vivo and in vitro biological properties, studies with this experimental model might easily and quickly provide some essential pieces of information.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a monoclonal antibody to L1210 leukaemia

Testorelli¹,

Morelli²,

Goldin³

et al. 1982

Summary.-A mouse monoclonal cell line (L1) was produced by fusing the mouse myeloma P3X63/Ag8 with CD2F1 spleen cells immunized with a highly immunogenic subline of L1210 leukaemia (Li210/DTIC). A very few positive clones (1%) were isolated and one of these was chosen for detailed study. The monoclonal antibody Li is an IgM immunoglobulin strongly reacting in a complement-dependent cytotoxicity assay against L1210/Cr leukaemia and its more or less inmmunogenic sublines. The specificity of the LI antibody against L1210 leukaemia was studied by extensive screening with normal adult and foetal tissues, lymphoid tissues from several independent strains and a panel of the most common experimental tumours, to all of which it was unreactive. Attempts at immunotherapy were carried out in DBA/2 mice challenged with L1210 leukaemia and treated with Li (ascites) and complement. Although the in vitro cytotoxic titre of ascites fluid from mice bearing hybridoma was very high (10-7), no therapeutic effect was obtained in vivo.

“…A number of claims (Kirch & Hammerling, 1981;Bernstein et al, 1980;Scheinberg & Strand 1982;Miller & Levy, 1981;Ritz et al, 1980;Trowbridge & Lopez 1982;Herlyn & Koprowski, 1981), of therapeutic benefit from the use of MAb in cancer therapy have been reported recently in the literature. Partial successes in tumour systems other than that used here could be attributed to different Ig isotypes, acting through an antibody-dependent cellular cytotoxicity (ADCC) rather than complement-mediated lysis.…”

Section: Discussionmentioning

confidence: 99%

Serotherapy of L1210 murine leukaemia—reasons for ineffectiveness of in vivo treatment by L.1 monoclonal antibody

Testorelli¹,

Canti²,

Franco³

et al. 1983

Summary A monoclonal antibody (L.1), reacting in vitro specifically with L1210 leukaemia cells in a complement-dependent cyctotoxicity assay (CDC), has been exploited for serotherapy studies. Different regimens of L.1 treatment of CD2F1 mice bearing the semi-syngeneic L1210 leukaemia did not prolong the life span of tumor-bearing animals. Moreover, the administration of L.1 did not enhance the antitumour effects of cyclophosphamide. Studies of in vivo localization showed that L.1 was able to bind specifically to L1210 leukaemic cells, although 30-40% of the cells remained negative. The presence of L.1 in mouse blood was demonstrated up to 15 days after the inoculation. On the other hand, in vivo administration of L.1 was probably accompanied by loss of the cytotoxic activity, perhaps through a mechanism of complement inactivation, since the presence of undiluted normal mouse serum in a CDC assay inhibited the cytotoxic activity of L.1. Moreover, serum from L.1-treated mice did not display any cytotoxic activity, although the presence of the antibody could be demonstrated by indirect immunofluorescence.Shedding of the antigen defined by L.1 was probably not responsible for the failure of the serotherapy, since the L. 1 neutralizing antigen could be found in body fluids only long after the start of therapy.