Module 9 2024

03/09/2024

Potential Immune Responses

Biotherapeutic in patient

non immunogenic (e.g., G-CSF, IFN  )

no effect (e.g., insulin, growth hormone)

immunogenic (induced antibodies - ADA )

alter PK/PD (e.g., immune-mediated clearance)

neutralise biological effects and compromise further therapy (e.g., factor VIII, IFN  2a)

Cross-react with native protein and induce adverse symptoms (e.g., Epo, MGDF)

Infusion reactions, anaphylactic reactions Delayed-type hypersensitivity

Consequences on efficacy - reduction or loss of clinical response to the biotherapeutic Consequences on safety - safety issues can occur even when there is no loss of efficacy

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Immunogenicity of Biotherapeutics: Examples

Antibody

Indication

Type of antibody

% ADA +ve patients

Product name®

OKT3

Allograft rejection

Murine

25

Bexxar

Non-Hodgkin lymphoma

Murine

11

Remicade

Crohn’s Disease & RA

Chimeric

10 - 60

Simulect

Transplant rejection

Chimeric

1 - 2

Rituxan

Non-Hodgkin lymphoma

Chimeric

11

Raptiva

Psoriasis

Humanized

6.3

CAMPATH

Leukemia

Humanized

50

Herceptin

Cancer

Humanized

<1

Humira

Crohn’s Disease, AS, RA

Fully-human

2.6 - 89

Casadevall et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med. 2002 Feb 14;346(7):469-75. doi: 10.1056/NEJMoa011931.

Vectibix

Colorectal cancer

Fully-human

4.6

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3