Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4

被引：26

作者：

Chauhan, Jitesh ^{[1
,2
]}

Grandits, Melanie ^{[1
]}

Palhares, Lais C. G. F. ^{[1
]}

Mele, Silvia ^{[1
]}

Nakamura, Mano ^{[1
]}

Lopez-Abente, Jacobo ^{[1
]}

Crescioli, Silvia ^{[1
]}

Laddach, Roman ^{[1
,3
]}

Romero-Clavijo, Pablo ^{[1
,4
]}

Cheung, Anthony ^{[1
,5
]}

Stavraka, Chara ^{[1
,2
,6
]}

Chenoweth, Alicia M. M. ^{[1
,5
]}

Sow, Heng Sheng ^{[1
]}

Chiaruttini, Giulia ^{[1
]}

Gilbert, Amy E. E. ^{[1
]}

Dodev, Tihomir ^{[7
,8
]}

Koers, Alexander ^{[9
]}

Pellizzari, Giulia ^{[1
]}

Ilieva, Kristina M. M. ^{[1
,5
]}

Man, Francis ^{[9
,10
]}

Ali, Niwa ^{[11
,12
]}

Hobbs, Carl ^{[13
]}

Lombardi, Sara ^{[1
,14
]}

Lionarons, Daniel A. ^{[4
]}

Gould, Hannah J. J. ^{[7
,8
]}

Beavil, Andrew J. J. ^{[7
,8
]}

Geh, Jenny L. C. ^{[15
,16
]}

Ross, Alastair D. MacKenzie D. ^{[15
]}

Healy, Ciaran ^{[15
]}

Calonje, Eduardo ^{[17
]}

Downward, Julian ^{[4
]}

Nestle, Frank O. O. ^{[1
,18
]}

Tsoka, Sophia ^{[3
]}

Josephs, Debra H. H. ^{[1
,2
,6
]}

Blower, Philip J. J. ^{[9
]}

Karagiannis, Panagiotis ^{[1
,19
]}

Lacy, Katie E. E. ^{[1
]}

Spicer, James ^{[2
,6
]}

Karagiannis, Sophia N. N. ^{[1
,5
]}

Bax, Heather J. J. ^{[1
,2
]}

机构：

[1] Kings Coll London, St Johns Inst Dermatol, Sch Basic & Med Biosci, London SE1 9RT, England

[2] Guys Hosp, Kings Coll London, Sch Canc & Pharmaceut Sci, London SE1 9RT, England

[3] Kings Coll London, Fac Nat Math & Engn Sci, Dept Informat, London WC2B 4BG, England

[4] Francis Crick Inst, Oncogene Biol Lab, 1 Midland Rd, London NW1 1AT, England

[5] Kings Coll London, Guys Hosp, Sch Canc & Pharmaceut Sci, Breast Canc Now Res Unit, London SE1 9RT, England

[6] Guys & St Thomas NHS Fdn Trust, Canc Ctr Guys, London SE1 9RT, England

[7] Kings Coll London, Randall Ctr Cell & Mol Biophys, Sch Basic & Med Biosci, London SE1 9RT, England

[8] Kings Coll London, Asthma UK Ctr, Allerg Mech Asthma, London SE1 9RT, England

[9] Kings Coll London, Sch Biomed Engn & Imaging Sci, London SE1 7EH, England

[10] Kings Coll London, Inst Pharmaceut Sci, Sch Canc & Pharmaceut Sci, London SE1 9NH, England

[11] Kings Coll London, Fac Life Sci & Med, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London SE1 9RT, England

[12] Kings Coll London, Fac Life Sci & Med, Ctr Gene Therapy & Regenerat Med, Sch Basic & Med Biosci, London SE1 9RT, England

[13] Kings Coll London, Wolfson Ctr Age Related Dis, London SE1 1UL, England

[14] Canc Ctr Guys, Guys & St Thomas Oncol & Haematol Clin Trials OHCT, London SE1 9RT, England

[15] Guys & St Thomas NHS Fdn Trust, Dept Plast Surg, London SE1 7EH, England

[16] Guys Hosp, St Johns Inst Dermatol, Skin Tumour Unit, London SE1 9RT, England

[17] St Thomas Hosp, St Johns Inst Dermatol, Dermatopathol Dept, London SE1 7EH, England

[18] Sanofi US, Cambridge, MA USA

[19] Univ Med Ctr Hamburg Eppendorf, Dept Oncol Haematol & Bone Marrow Transplantat, Hamburg, Germany

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

“创新英国”项目; 英国医学研究理事会;

关键词：

BASOPHIL ACTIVATION TEST; MONOCLONAL-ANTIBODIES; DISTINCT DETERMINANTS; IMMUNOGLOBULIN-E; SOLID TUMORS; IN-VITRO; CANCER; IMMUNOTHERAPY; CELLS; CYTOTOXICITY;

D O I：

10.1038/s41467-023-37811-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is similar to 70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma. CSPG4 IgE binds to human melanomas including metastases, mediates tumoricidal antibody-dependent cellular cytotoxicity and stimulates human IgE Fc-receptor-expressing monocytes towards pro-inflammatory phenotypes. IgE demonstrates anti-tumor activity in human melanoma xenograft models engrafted with human effector cells and is associated with enhanced macrophage infiltration, enriched monocyte and macrophage gene signatures and pro-inflammatory signaling pathways in the tumor microenvironment. IgE prolongs the survival of patient-derived xenograft-bearing mice reconstituted with autologous immune cells. No ex vivo activation of basophils in patient blood is measured in the presence of CSPG4 IgE. Our findings support a promising IgE-based immunotherapy for melanoma.

引用

页数：18

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