Immunological Methods to Study Monoclonal Antibody Activity in Chronic Lymphocytic Leukaemia

Methods Mol Biol. 2019:1881:173-184. doi: 10.1007/978-1-4939-8876-1_14.

Abstract

Over recent decades it has become increasingly apparent that malignant cells, including chronic lymphocytic leukemia (CLL) cells, do not exist in isolation. Rather they coalesce with numerous "normal" cells of the body and, in the case of CLL, inhabit key immunological niches within secondary lymphoid organs (SLO), where a plethora of stromal and immune cells mediate their growth and survival. With the advent and approval of targeted immune therapies such as monoclonal antibodies (mAb), which elicit their efficacy by engaging immune-mediated effector mechanisms, it is important to develop accurate methods to measure their activities. Here, we describe a series of reliable assays capable of measuring important antibody-mediated effector functions: antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) that measure these immune activities.

Keywords: Antibody-dependent cellular cytotoxicity (ADCC); Antibody-dependent cellular phagocytosis (ADCP); Complement-dependent cytotoxicity (CDC); Monoclonal antibodies (mAb); Secondary lymphoid organs (SLO).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Cell Line
  • Coculture Techniques
  • Cytotoxicity Tests, Immunologic / instrumentation
  • Cytotoxicity Tests, Immunologic / methods*
  • Drug Screening Assays, Antitumor / instrumentation
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Macrophages
  • Mice
  • Monocytes
  • Phagocytosis / drug effects
  • Phagocytosis / immunology
  • Primary Cell Culture / instrumentation
  • Primary Cell Culture / methods

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological