Natural killer (NK) cell function is a strong prognostic factor in colorectal carcinoma patients treated with the monoclonal antibody 17-1A.
Tumor cells might be susceptible to different effector functions of the immune system. This cytotoxic capacity has been utilized to analyze the prognostic significance of peripheral blood mononuclear cells (PBMC) in patients with metastatic colorectal carcinoma (CRC) treated with the monoclonal antibody (MAb)17-1A. Such analysis might form the basis for future patient selection and may lead to improvements in therapeutic strategies. Between 1986 and 1998, 73 patients were treated with regimens containing MAb17-1A. Prior to therapy, the lytic capability of PBMC was assayed against: K562 (4 hr assay), the CRC cell line SW948 (4 hr and 18 hr assays) and antibody-dependent cellular cytotoxicity (ADCC, 18 hr assay). Since the study was performed over 13 years, the assays were checked for time-related bias. Reproducibility over time was satisfactory. Patients exhibited a significantly higher cytotoxic capability in all 4 assays compared to healthy control donors. No correlation to clinical outcome was noted for 18 hr ADCC and 18 hr spontaneous cytotoxicity. Pretreatment natural killer (NK) cell cytotoxicity (K562) was significantly related to overall survival (OS), progression-free survival (PFS), and response rate. OS for patients with high and low NK cell cytotoxicity was 71 vs. 30 weeks, respectively (p = 0.007). NK cell cytotoxicity (K562) was an independent prognostic factor for OS (p = 0.016). Pretreatment NK cell activity is a strong prognostic factor for patients with metastatic CRC receiving MAb17-1A therapy and is a predictor for OS, PFS and response. These results should be considered when designing antibody-based therapeutic protocols.
Department of Oncology (Radiumhemmet), Karolinska Hospital, SE-171 76 Stockholm, Sweden.
Maria
M
Liljefors
Bo
B
Nilsson
Anna-Lena
AL
Hjelm Skog
Peter
P
Ragnhammar
Håkan
H
Mellstedt
Jan-Erik
JE
Frödin
D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D012004:Rectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D015203:Reproducibility of Results; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C050928:carcinoma-associated antigen 17-1A