Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines.
The therapy of colorectal cancer may be improved by biologic response modifiers that enhance natural killer (NK) cell and antibody-dependent tumoricidal mechanisms. This study examined the effect of a recently discovered cytokine purified from the supernatant of an Ebstein-Barr virus-transformed B-lymphoblastoid cell line (RPMI-8866), natural killer cell stimulatory factor (NKSF), on NK and antibody-dependent cellular cytotoxicity (ADCC) of human colon adenocarcinoma cell lines. Human peripheral blood lymphocytes were cultured for 24 hr in the presence or absence of NKSF (3.6 pM) or interleukin-2 (1 nM). The cultured lymphocytes were analyzed for lytic potential toward chromium-51-labeled colon carcinoma targets SW 1116, 498 LI, and WC 1. ADCC was measured by incubating chromium-51-labeled SW 1116 or WC 1 targets with the monoclonal antibody CO17-1A, an IgG2a antibody reactive with gastrointestinal cancer-associated cell antigen, or control mouse IgG prior to testing NKSF-treated or control PBL effectors in a 6-hr cytotoxicity assay. NKSF significantly enhanced NK cytolysis of colon carcinoma and NK-resistant lymphoma cell lines, and on a molar basis was approximately 300 times more potent than interleukin-2 in generating NK cytotoxicity. Furthermore, NKSF significantly augmented lymphocyte-mediated ADCC against colon carcinoma targets, and the combination of NKSF with the antibody CO17-1A had an additive effect on lymphocyte tumoricidial capacity. Thus, NKSF may have a potential role in the treatment of colon cancer.
Lieberman
M D
MD
Department of Surgical Research, University of Pennsylvania, School of Medicine, Philadelphia 19104.
Sigal
R K
RK
Williams
N N
NN
Daly
J M
JM
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D018664:Interleukin-12; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011961:Receptors, Fc / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D007378:Interleukins; D011961:Receptors, Fc; D018664:Interleukin-12