IgE antibodies against cancer: efficacy and safety

TY - JOUR

T1 - IgE antibodies against cancer: efficacy and safety

AU - Chauhan, Jitesh

AU - McCraw, Alexa J

AU - Nakamura, Mano

AU - Osborn, Gabriel

AU - Sow, Heng Sheng

AU - Stavraka, Chara

AU - Josephs, Debra

AU - Spicer, James

AU - Karagiannis, Sophia N

AU - Bax, Heather

N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to anti-parasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumors. This has lead to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here we bring together the properties of IgE antibodies pivotal to the hypothesis for superior anti-tumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anti-cancer IgE therapeutic.

AB - Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to anti-parasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumors. This has lead to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here we bring together the properties of IgE antibodies pivotal to the hypothesis for superior anti-tumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anti-cancer IgE therapeutic.

KW - AllergoOncology

KW - Anaphylaxis

KW - Antibodies

KW - Basophil activation test (BAT)

KW - Cancer

KW - IgE

KW - Immunotherapy

KW - In vivo models

KW - Safety

KW - Type I hypersensitivity

UR - http://www.scopus.com/inward/record.url?scp=85106143872&partnerID=8YFLogxK

U2 - 10.3390/antib9040055

DO - 10.3390/antib9040055

M3 - Review article

AN - SCOPUS:85106143872

SN - 2073-4468

VL - 9

SP - 1

EP - 27

JO - Antibodies (Basel, Switzerland)

JF - Antibodies (Basel, Switzerland)

IS - 4

M1 - 55

ER -