Module 9 2024

03/09/2024

Monoclonal antibodies (mAbs) are typically an IgG • IgGs are comprised of 4 main types → IgG1, IgG2, IgG3 and IgG4 • IgG1 and IgG4 are the most commonly used formats for biotherapeutics

Antigen binding site

Parameter

IgG1

IgG2

IgG3

IgG4

Heavy chain

Molecular Mass (kD)

146

146

170

146

Complement activation (C1q binding)

++

+

+++

-

Light chain

Fc γ R1*

6500

-

6100

3400

Fc γ R2a*

520

45

89

17

Fc Region

Fc γ R2b*

12

2

17

20

Fc γ R3a*

200

7

980

25

* = Binding in uM; Table modified from Yu et al (2020) J Hematol Oncol, 13: Article 45

• IgG1 has highest affinity for all FcγRs → Potent activator of ADCC and ADCP • IgG4 has high affinity for FcγRI but not others → Weak activator of ADCC and ADCP Which IgG is chosen depends on MoA and whether ADCC and ADCP are desirable or not

ADCC = antibody dependent cell mediated cytotoxicity; ADCP = antibody dependent cellular phagocytosis

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Monoclonal antibody related formats – some examples • Variable and becoming more exotic…. • Design dependent on many factors, e.g. target organ accessibility, potential structure-related toxicities and MoA

Antigen binding site

Heavy chain

Light chain

Fc Region

Bispecific antibody

Figure modified from Schweizera et al (2014). European Journal of Pharmaceutics and Biopharmaceutics, 88, Pages 291-309

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Preclinical Testing of Biologicals – Sept 2024

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