1991; Fig. 22.1). The basic design issues involved in the CDR-grafting methodology

are (1) defining CDRs of the donor antibody that needs to be grafted, (2) source of

human light- and heavy-chain sequences to be used for CDR grafting, and (3) careful

selection of the residues outside CDRs that are critical for antibody specificity and

binding to the target antigen and their back mutation in human sequence to restore or

improve the affinity of the humanized antibody. The experimental structure of the

murine antibody in complex with the antigen can provide a detailed map of amino

acid residues in contact with the antigen and thus facilitate determining the regions to

be grafted. However, at the beginning of the humanization protocol, only on rare

occasions the experimental structure of the antibody is known. In the absence of such

precise definition of antibody residues responsible for specificity, CDRs have been

Table 22.1 Partial list of chimeric MAbs approved for therapeutic applications in humans

Product

Trade

name

Indication

Target

Company (FDA

approval)

Abciximab

ReoPro^®

High-risk angioplasty

(prevention of blood

clots)

Glycoprotein

IIb/IIIa

receptor on

platelet

Centocor Ortho

Biotech

(Johnson &

Johnson), Eli

Lilly (1994)

Rituximab

Rituxan^®

Non-Hodgkin’s

lymphoma, chronic

lymphocytic leukemia,

rheumatoid arthritis

CD20

Genentech

(Roche) (1997)

Basiliximab

Simulect^®

Transplant rejection

CD25

(a chain of

IL-2 receptor)

Novartis (1998)

Infliximab

Remicade^®

Rheumatoid arthritis,

Crohn’s disease,

psoriasis, ulcerative

colitis

TNF-α

Centocor Ortho

Biotech

(Johnson &

Johnson) (1998)

Cetuximab

Erbitux^®

Colorectal cancer, head

and neck cancer

EGFR

Merck Serono/

Bristol Myers

Squibb/ImClone

(Eli Lilly)

(2004)

Siltuximab

Sylvant^®

Giant lymph node

hyperplasia

cCLB8

Janssen-Cilag

International

(2014)

Obiltoxaximab

Anthim^®

Anthrax infection

PA

component of

B. anthracis

toxin

Elusys

Therapeutics,

Inc. (2016)

Infliximab

Inflectra^®

Ankylosing spondylitis,

rheumatoid arthritis,

ulcerative colitis,

psoriatic arthritis,

Crohn’s disease, psoriasis

TNF-α

Hospira UK

Limited (2016)

404

S. K. Gupta and P. Chaudhary