Expression of the OKT monoclonal antibody defined antigenic determinants in malignancy

Melvyn Greaves, Domenico Delia, Robert Sutherland, Jagdish Rao, Winston Verbi, John Kemshead, Gita Hariri, Gideon Goldstein, Patrick Kung

Research output: Contribution to journalArticlepeer-review

Abstract

Monoclonal antibodies OKT1,3,4,6,8,9,10,11 and 11A have been screened by immunofluorescence (FACS and microscopy) and 125I-binding assays for their cellular specificity in human leukaemia in relation to other cell markers (e.g. cALL gp100 antigen, HLA-DR, TdT, E rosettes). In a series of 69 T cell malignancies a distinctive correlation was observed between phenotype and clinical diagnosis. In every instance, T-ALL cells have an immature or early thymic phenotype and T non-Hodgkin lymphoma have a predominant cortical thymic phenotype indicating that these two malignancies originate from T cell precursors. In contrast, adult T-Sezary leukaemia, T-CLL and T-PLL have mature T cell subset phenotypes, the majority being T3+ T4+ T8- /TdT- "helper/inducer" cell types and are presumed to originate in mature immunocompetent T cells. OKT11 and OKT11A give concordant reactions with E (sheep) rosettes and appear to react with the same receptor structure. The composite phenotype of several T-ALL cell lines can be modulated in vitro by phorbol ester (TPA). HPB-ALL, for example, loses TdT and OKT4 binding, decreases OKT9, maintains OKT8 and increases OKT1, HLA-ABC and OKT11 binding and E rosettes. OKT9 reacts preferentially in T leukaemias with T-ALL but is not T specific. It binds to many types of leukaemias and to malignant cell lines e.g. teratocarcinoma, melanoma, colon carcinoma and neuroblastoma. Normal foetal thymus, foetal liver and lectin activated T cells are also positive. Cell separation experiments indicate that OKT9 determinant is clearly associated with cell proliferation status although not cycle phase specific. When leukaemic cells (such as HL-60, HPB-ALL) are induced to mature in vitro by retinoic acid or TPA, respectively, the OKT9 determinant is lost. Biochemical studies indicate that OKT9 reacts with a gp 90K dalton dimer which appears to be the receptor for transferrin. This monoclonal antibody defined structure is probably the same as that described by Onary with monoclonal B3/25 and by Bramwell and Harris. The latter believed the structure to be a specific marker of malignancy. Some other OKT monoclonals are not T lineage specific. OKT10 binds to leukaemias and normal marrow cells of the myeloid and B cell lineages. OKT6 binds to neuroblastoma cells as does a similar monoclonal, NA134/HTA-1.

Original languageEnglish
Pages (from-to)283-299
Number of pages17
JournalInternational Journal of Immunopharmacology
Volume3
Issue number3
DOIs
Publication statusPublished - 1981

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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