| Abstract: |
JD118 is a murine immunoglobulin M monoclonal antibody (mAb) under study as a therapeutic agent that is capable of potent human complement-mediated cytotoxicity (CMC) against B-cell lymphoma and leukemia targets. The JD118 antigen target was upregulated on fresh human B cells and B-cell neoplasms after brief in vitro incubation in media containing calf serum. To determine if cytokines could also lead to upregulation of JD118 antigen, alpha-interferon (α-IFN), gamma-interferon (γ-IFN), interleukin 2 (IL-2), or IL-4 were added to fresh neoplastic B cells in serum-free media and changes in JD118 antigen expression were evaluated by flow cytometry (FCM). IL-4 was found to be the predominant cytokine responsible for inducing upregulation of the JD118 antigen. Marked JD118 upregulation by IL-4 was seen in 14 out of 14 chronic lymphocytic leukemia (CLL) samples tested, with 50 to 750-fold increases in four samples, 11 to 49-fold increases in four samples, and up to 10-fold increase in six samples. One B-cell lymphoma specimen was upregulated 18-fold, but no upregulation was demonstrated in one hairy cell leukemia and two acute myelogenous leukemia specimens tested. The specificity of the IL-4 upregulation was demonstrated by the elimination of its activity by blocking with a neutralizing anti-IL-4 mAb. IL-4 upregulation allows JD118 mAb CMC against otherwise antigen-negative targets and argues for phase I trials using a combination of IL-4 cytokine and mAb for B-cell neoplasms. |
| Keywords: |
controlled study; unclassified drug; acute granulocytic leukemia; human cell; alpha interferon; flow cytometry; antigen expression; cell survival; interleukin 2; interleukin 4; monoclonal antibody; b cell lymphoma; cytokine; antibodies, monoclonal; immunotherapy; gamma interferon; membrane glycoproteins; target cell; antigens, cd; up-regulation; chronic lymphatic leukemia; antigens, cd19; antigens, surface; complement dependent cytotoxicity; immunoglobulin m antibody; hairy cell leukemia; b cell leukemia; interleukin-4; leukemia, lymphocytic, chronic; antigens, differentiation, b-lymphocyte; antibody-dependent cell cytotoxicity; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; jd 118
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