1644PD - Antibody-dependent cell-mediated cytotoxicity (ADCC) evolution under treatment by cetuximab and links with treatment outcome in locally advanced hea...

Date 29 September 2012
Event ESMO Congress 2012
Session Basic Science and Translational Research I
Topics Colon Cancer
Rectal Cancer
Head and Neck Cancers
Translational Research
Presenter Cristiana Lo Nigro
Authors C. Lo Nigro1, M. Monteverde1, G. Strola2, M. Maffi1, E. Miraglio1, L. Lattanzio1, D. Vivenza1, F. Messa1, G. Milano3, M.C. Merlano1
  • 1Oncology, S. Croce General Hospital, 1200 - Cuneo/IT
  • 2Laboratory, S. Croce General Hospital, 12100 - Cuneo/IT
  • 3Oncopharmacology Unit, Lacassagne, 06100 - Nice/FR

Abstract

Background

ADCC may play a role in antitumor activity of IgG1 mAb by inducing immune cell-mediated tumor lysis. We evaluated ADCC ability before and under cetuximab treatment and impact on survival in locally advanced Head and Neck (LAHNSCC) or metastatic colorectal cancer (mCRC).

Methods

82 patients (60 men, 22 women; median age 64, range 39-87), 39 LAHNSCC and 43 mCRC, treated with chemotherapy (irinotecan or folfiri) plus cetuximab, were prospectively enrolled. ADCC ex-vivo was measured before treatment and every 2 months (1 to 7 measurements/patient, 44 patients with ≥2 measurements). 400 000 purified Natural Killer cells (CD3- CD56+) from patients were incubated with 10 000 target cells (CAL166 cell line expressing EGFR) and 10 µg/ml cetuximab. Cytotoxicity was measured by LDH-release assay. ADCC was expressed as % of lysed target cells. Polymorphisms of Fcg receptors FcgR2a (131Arg > His) and FcgR3a (158Phe > Val) were analyzed by Allelic Discrimination assay.

Results

The feasibility rate of ADCC measurements was 85-90%. Basal ADCC ranged between 30% and 100% (mean 62%, median 66%) and was not influenced by gender. A trend for an increased basal ADCC was observed in younger patients: median was 66% in the 22 patients < 65 vs 56% in the 22 patients ≥ 65 years (p = 0.084), with a marked difference by tumour site (H&N p = 0.056; colon p= 0.16). FcgR2a and FcgR3a gene polymorphisms were not linked to basal ADCC. The evolution of individual ADCC ability before treatment and 2 months later revealed a significant drop in ADCC (intra-patient comparison, N = 44, p = 0.003, absolute median drop of 20%). 82 patients were assessable for survival (43 deaths; median follow up = 10.3 month). Cutaneous rash, but not basal ADCC, was related to survival (p = 0.043). There were no correlation between ADCC evolution (decrease/increase during the two months) vs EGFR status nor vs cutaneous rash.

Conclusions

A new generation of mAb is currently being developed with the aim to amplify ADCC. Present data illustrate the feasibility of ADCC measurement in mAb-treated patients and reveal an initial drop in ADCC under treatment that may reflect the variable chemotherapy-induced impact on host immunity.

Disclosure

All authors have declared no conflicts of interest.