Module 9 2024

03/09/2024

Definitions

Immunogenicity: ability of a particular substance to elicit an immune response.

If there is an induced immune response in patient, the substance is said to be immunogenic and is designated as the antigen.

Immune response: humoral (production of antibodies) and/or cell-mediated.

Epitope (determinant or antigenic determinant) : part of the antigen recognised by the immune system. Epitopes can be linear or conformational and combine with the specific antibodies produced.

Distinction between sought-after immunogenicity (e.g., vaccines – inducing immune response aiming at protecting the individual) and unwanted immunogenicity (e.g., biotherapeutics - production of anti drug antibodies or ADA).

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Biotherapeutics

Recombinant proteins – include sequence variants, chemical modifications, hybrid molecules, … • Hormones, Enzymes, Cytokines • Monoclonal antibodies

Murine mAb “ - omab”

Chimeric mAb murine variable domain “ - iximab”

Humanized mAb murine CDR sequences “ - zumab”

Fully human mAb “ - umab”

potential for immunogenicity

• Antibody-derived molecules: many formats e.g., fusion proteins, multi-domain biotherapeutics (MDB) - bispecific Abs, antibody-drug conjugates (ADC), nanobodies • Newer modalities: oligonucleotide-based therapeutics, RNA-based therapeutics, gene therapy, cell therapy (e.g., CAR-T cell)

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