Antibody Injection Therapy may Provide Long-term Immunoprotection against Cancer

Scientists from Rockefeller University applied a tumor specific antigen model to analyze if passive antibiotic injection could cause the sequential immunoreaction. This study was published in Cell.

Passive administration of anti-tumor antibodies is an important clinical tool for the management of a variety of cancers and generally functions by targeting malignant cells through Fc-receptor for IgG(FcγR)-mediated antibody-dependent cellular cytotoxicity(ADCC) by myeloid effector cells or possibly natural killer (NK) cells. However, anti-tumor mAb treatment can also induce a vaccinal effect, in which mAb-mediated tumor death induces a long-term antitumor cellular immune response.

19CDB21B-108D-4AF7-A3D7-D87ED88174D7

New technologies have enabled the identification of tumor mutational signatures, some common across multiple cancer types while others are restricted to specific malignacies. Thus, mutation-induced, developmentally restricted, or overexpressed tumor neoantigens are a major
target of tumor-infiltrating lymphocytes in patients

Three activating FcγRs are expressed in mice (mouseFcγRI, mFcγRIII, and mFcγRIV) and humans (hFcγRI,hFcγRIIA, and hFcγRIIIA), and a single inhibitory FcγR, FcγRIIB, is expressed in both species. The cellular outcome of IgG interactions with FcγRs is governed by the affinity of an antibody’s Fc for the specific receptor and the expression pattern of those receptors on effector cells

In this study, to determine how such responses are generated, scientists utilized a murine model of an anti-tumor vaccinal effect against a model neoantigen. They demonstrate that FcγR expression by CD11c+ antigen-presenting cells is required to generate antitumor T cell responses upon ADCC-mediated tumor clearance. Using FcgR-humanized mice, we demonstrate that anti-tumor human (h)IgG1 must engage h FcγR IIIA on macrophages to mediate ADCC, but also engage h FcγR IIA, the sole h FcγR expressed by human dendritic cells (DCs), to generate a potent vaccinal effect. Thus, while next-generation antitumor antibodies with enhanced binding to only h FcγR IIIA are now in clinical use, ideal anti-tumor antibodies must be optimized for both cytotoxic effects as well as h FcγR IIA engagement on DCs to stimulate long-term anti-tumor cellular immunity.

Reference:

DiLillo D J, Ravetch J V. Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal Effect[J]. Cell, 2015, 161(5): 1035-1045.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>