Anti-GD2 IgA kills tumors by neutrophils without antibody-associated pain in the preclinical treatment of high-risk neuroblastoma.

ABSTRACT:

Background

The addition of monoclonal antibody therapy against GD2 to the treatment of high-risk neuroblastoma led to improved responses in patients. Nevertheless, administration of GD2 antibodies against neuroblastoma is associated with therapy-limiting neuropathic pain. This severe pain is evoked at least partially through complement activation on GD2-expressing sensory neurons.

Methods

To reduce pain while maintaining antitumor activity, we have reformatted the approved GD2 antibody ch14.18 into the IgA1 isotype. This novel reformatted IgA is unable to activate the complement system but efficiently activates leukocytes through the FcαRI (CD89).

Results

IgA GD2 did not activate the complement system in vitro nor induced pain in mice. Importantly, neutrophil-mediated

SUBMITTER: Evers M 

PROVIDER: S-EPMC8559241 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature