In vitro tests that predict tumor-associated idiotype levels in the serum
of patients with B cell lymphomas and leukemias
RA Miller, JN Lowder, J Gralow, T Meeker and R Levy
The presence of circulating tumor idiotype interferes with the in vivo
effectiveness of anti-idiotype antibodies. We developed two assays that
permit identification of patients with high levels of serum idiotype
without the need for first producing an anti-idiotype antibody. A cell
suspension made from the tumor was cultured for seven days with or without
phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion
in vitro by patients' tumor cells varied. In 4 patients, no secretion in
vitro occurred, 5 patients had low levels, and 5 patients had high levels
of Ig secretion. In three patients, Ig secretion occurred only after
stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin
secretion in vitro is related to the levels of tumor idiotype secretion
that exist in vivo. Eight patients with serum idiotype levels greater than
100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0
microgram/10(6) cells of idiotype secretion in vitro. Nine patients with
serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL),
had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion
in vitro. In another assay, the levels of IgM kappa and IgM lambda in
patients' sera were compared with those in normal serum. An imbalance in
the relative amounts of IgM kappa and IgM lambda indicated high levels of
circulating idiotype in the serum, but this assay was less sensitive than
the in vitro secretion assay and limited to IgM-secreting tumors. These
assays will be useful for future clinical studies using anti- idiotype
antibodies.
Volume 69,
Issue 4,
pp. 1249-1254,
04/01/1987
Copyright © 1987 by The American Society of Hematology