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Follicular lymphoma and the immune system: from pathogenesis to antibody therapy

Follicular lymphoma and the immune system: from pathogenesis to antibody therapy
Follicular lymphoma and the immune system: from pathogenesis to antibody therapy
Follicular lymphoma (FL) is a B-cell tumor arising in germinal centers and retaining features of its normal B-cell counterpart. Lymphomagenesis appears stepwise from the t(14;18) translocation, through FL-like cells, to FL in situ, then to overt FL. Surface Ig is mandatory and carries a striking V-region modification because of introduction of glycan addition sites during somatic mutation. These are positively selected and acquire unusual high mannoses, which interact with lectins. The Ig-associated mannoses appear essential for FL, providing a disease- specific target for antibody attack. Antibody therapy is currently focused on anti-CD20 (rituximab), which appears to rely predominantly on the Fc? module recruiting suitably activated macrophages. Immunogloblulin and, to some extent, CD20, can each escape antibody attack in vitro by modulation, but this is difficult to demonstrate clinically. Instead, studies of anti-CD20 therapy of FL suggest that effector modulation, similar to that seen in the suppression of autoimmune inflammation by infusions of normal human IgG, may be important. Both antigenic and effector modulations might be minimized by repeated small doses of more potent antibodies. Clearly, mechanisms of attack vary with the malignancy, the target molecule, and the antibody design, offering opportunities for optimizing this promising strategy.
0006-4971
3659-3667
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Stevenson, George T.
5bed316c-8332-4cdb-b351-2f7615ecb9bb
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Stevenson, George T.
5bed316c-8332-4cdb-b351-2f7615ecb9bb

Stevenson, Freda K. and Stevenson, George T. (2012) Follicular lymphoma and the immune system: from pathogenesis to antibody therapy. Blood, 119 (16), 3659-3667. (doi:10.1182/blood-2011-11-367730). (PMID:22337721)

Record type: Article

Abstract

Follicular lymphoma (FL) is a B-cell tumor arising in germinal centers and retaining features of its normal B-cell counterpart. Lymphomagenesis appears stepwise from the t(14;18) translocation, through FL-like cells, to FL in situ, then to overt FL. Surface Ig is mandatory and carries a striking V-region modification because of introduction of glycan addition sites during somatic mutation. These are positively selected and acquire unusual high mannoses, which interact with lectins. The Ig-associated mannoses appear essential for FL, providing a disease- specific target for antibody attack. Antibody therapy is currently focused on anti-CD20 (rituximab), which appears to rely predominantly on the Fc? module recruiting suitably activated macrophages. Immunogloblulin and, to some extent, CD20, can each escape antibody attack in vitro by modulation, but this is difficult to demonstrate clinically. Instead, studies of anti-CD20 therapy of FL suggest that effector modulation, similar to that seen in the suppression of autoimmune inflammation by infusions of normal human IgG, may be important. Both antigenic and effector modulations might be minimized by repeated small doses of more potent antibodies. Clearly, mechanisms of attack vary with the malignancy, the target molecule, and the antibody design, offering opportunities for optimizing this promising strategy.

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More information

Published date: 19 April 2012
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 348419
URI: https://eprints.soton.ac.uk/id/eprint/348419
ISSN: 0006-4971
PURE UUID: 92ce3f35-fbf1-4419-9be3-7fdb866fb441
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

Catalogue record

Date deposited: 13 Feb 2013 12:39
Last modified: 06 Jun 2018 13:01

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