Combining expression of GPC3 in tumors and CD16 on NK cells from peripheral blood to identify patients responding to

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Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK Cells
10:44

Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK Cells

Published on: February 2, 2011

49.6K

Gong Chen1, Ya-Chi Chen1, Bernhard Reis2

  • 1Roche Pharmaceutical Research and Early Development, Roche Innovation Center New York, New York, NY, USA.

Oncotarget
|March 15, 2018
PubMed
Abstract

Insights

Codrituzumab efficacy in advanced hepatocellular carcinoma (HCC) requires both high tumor glypican-3 (GPC3) and high CD16 on NK cells. Lacking either biomarker negates therapeutic benefit, suggesting a composite biomarker approach.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Codrituzumab is a monoclonal antibody targeting glypican-3 (GPC3) on hepatocellular carcinoma (HCC) cells.
  • It induces antibody-dependent cellular cytotoxicity (ADCC) and inhibits tumor growth in preclinical models.
  • The study investigated tumor GPC3 and NK cell CD16 expression as potential biomarkers for codrituzumab efficacy.

Purpose of the Study:

  • To correlate tumor GPC3 expression and NK cell CD16 expression with codrituzumab's clinical efficacy in advanced HCC patients.
  • To identify a composite biomarker for selecting patients who may benefit from codrituzumab treatment.

Main Methods:

  • Analysis of data from a phase II clinical trial of codrituzumab.
  • Quantification of GPC3 expression in tumor biopsies via immunohistochemistry (IHC).
  • Assessment of CD16 expression on NK cells using peripheral blood lymphocyte immunophenotyping.

Main Results:

  • Joint analysis revealed that high GPC3 expression and high CD16 expression were both necessary for patients to benefit from codrituzumab.
  • The absence of either high GPC3 or high CD16 expression resulted in a loss of therapeutic effect.

Conclusions:

  • The combination of high tumor GPC3 expression and high baseline CD16 expression on NK cells serves as a composite biomarker for selecting HCC patients for codrituzumab therapy.
  • Future studies are warranted in HCC patients with both high GPC3 and high CD16 to confirm codrituzumab's therapeutic benefit.
Keywords:
GC33 monoclonal antibodyNK cellantibody-dependent cellular cytotoxicity (ADCC)hepatocellular carcinomapredictive biomarker

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