The production and application of non-rodent monoclonal antibodies in veterinary science

Abstract

The requirement for monoclonal antibodies derived from species other than rats and mice is becoming increasingly realised in veterinary, as well as human, medicine. This paper reviews current knowledge of the production of inter-species hybridomas (heterohybridomas) by the fusion of rodent myeloma cell lines with lymphocytes from species of veterinary importance. To date a number of monoclonal immunoglobulins derived from sheep, cattle, pig, rabbit, mink and primate species have been produced to a variety of different bacterial, viral and nematode pathogens as well as to blood group and MHC determinants and to hormones. The technique opens up a number of possibilities for the future; some of these applications are discussed in relation to the antibodies produced thus far.

Review: Veterinary Sources of Nonrodent Monoclonal Antibodies: Interspecific and Intraspecific Hybridomas

“…Greater hope lies in the isolation of suitable naturally occurring lymphoblastoid tumours for sensitization. Such lines have been reported in humans, horses, cats, cattle, (116) and pigs. (117) …”

“…For example, sheep, 3.3 3 10 2 11 M to 3.8 3 10 2 16 M (20,21,95) ; cattle, 5.33 3 10 2 10 M and 2.5 3 10 2 11 M (46,97) ; pig, 8.3 3 10 2 12 and 8.3 3 10 2 1 3 M (54) ; and chimpanzee, 3.3 3 10 2 13 M. (98) To some extent, this difference in affinities may reflect the better polyclonal response of certain nonmurine species to particular antigens. (116) …”

The preparation of an ovine monoclonal antibody to progesterone

“…Consequently, the loss of antibody-secreting cell lines can be very marked during the initial post-fusion phase (Groves & Tucker, 1989). It is unusual to isolate successfully large numbers of suitable clones from interspecific fusions.…”

“…It was intended to immortalize, and perhaps improve, the characteristics of these antibodies by using the animals producing the antisera as sources of sensitized lympho¬ cytes for the production of ovine anti-progesterone MAbs. Although there have been several reports of ovine MAb-secreting cell lines established using inter¬ specific fusion techniques (Groves & Tucker, 1989), most of these lines have subsequently proved to be unstable in long-term culture. The production of ovine MAbs appears to present greater problems than those encountered in the generation of bovine MAbs.…”

Generation of native bovine mAbs by phage display

“…One area that typifies this difficulty is that of mAb technology, originally described for the production of murine Igs through the generation of hybridoma cells (1). Although attempts to produce monospecific human antibodies by other immortalization methods, for example by transformation with Epstein-Barr virus (2), have met with success, it has proved difficult to apply this strategy to large domesticated animals of economic significance, especially cattle, where there have been only isolated reports of the generation of mAbs through the formation of heterohybridoma lines of uncertain stability (3,4). The advent of antibody phage-display technology, where specific mAbs are generated by using molecular cloning techniques (5,6), offers the opportunity to redress this constraint, because the methods that ultimately yield mAbs are founded on an understanding of the molecular immunology of the species under study, rather than the availability of stable transformed cell lines or methods to immortalize B lymphocytes.…”