Pentosanpolysulfate Mitigates Neurological Adverse Effects in CD3 Bispecific Antibody Therapy
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Solution Overview
Problem
Antibody-based cancer therapies, such as those using CD19xCD3 bispecific antibodies, often cause neurological adverse effects like cytokine release syndrome and CNS reactions, which can be severe and life-threatening, limiting their tolerability and efficacy.
Innovation Solution
Administering pentosanpolysulfate (PPS) prior to, concurrently with, or after the CD3 binding domain therapy to mitigate or prevent neurological adverse effects, as PPS has been shown to alleviate or prevent these reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CD3 binding domain therapy is administered to treat cancer, then therapeutic efficacy is improved, but neurological adverse effects occur
Solution Approach 1:
Pentosanpolysulfate (PPS) is introduced as an intermediary substance that mediates between the CD3 binding domain therapy and the patient's nervous system. PPS binds to the CD3 binding domain or its complexes, preventing direct interaction with neural tissues while maintaining the therapeutic anti-cancer activity, thus reducing neurological adverse effects without compromising treatment efficacy
Solution Approach 2:
Pentosanpolysulfate is administered prior to or concurrently with the CD3 binding domain therapy to establish protective coverage in advance. This pre-cushioning approach creates a protective environment that prevents neurological adverse effects from occurring in the first place, rather than treating them after they manifest
Data Source
AI summary
The present invention relates to a pentosanpolysulfate (PPS) or a pharmaceutically acceptable salt thereof for use in the amelioration, treatment, or prevention of adverse neurological events caused by administering an antibody or fragment thereof comprising a CD3 binding domain, including a CD19 x CD3 bispecific single chain antibody, such as blinatumomab. PPS is a semi-synthetically produced heparin-like macromolecular carbohydrate derivative, which chemically and structurally resembles glycosaminoglycans. Kits comprising a PPS, an antibody or fragment thereof comprising a CD3 binding domain, and instructions for administration, which indicate that the PPS is to be employed for the amelioration, treatment or prevention of adverse neurological events caused by administering the antibody or fragment thereof comprising said CD3 binding domain, are also disclosed.