Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4
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Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4. / Chauhan, Jitesh; Grandits, Melanie; Palhares, Lais C G F; Mele, Silvia; Nakamura, Mano; López-Abente, Jacobo; Crescioli, Silvia; Laddach, Roman; Romero-Clavijo, Pablo; Cheung, Anthony; Stavraka, Chara; Chenoweth, Alicia M; Sow, Heng Sheng; Chiaruttini, Giulia; Gilbert, Amy E; Dodev, Tihomir; Koers, Alexander; Pellizzari, Giulia; Ilieva, Kristina M; Man, Francis; Ali, Niwa; Hobbs, Carl; Lombardi, Sara; Lionarons, Daniël A; Gould, Hannah J; Beavil, Andrew J; Geh, Jenny L C; MacKenzie Ross, Alastair D; Healy, Ciaran; Calonje, Eduardo; Downward, Julian; Nestle, Frank O; Tsoka, Sophia; Josephs, Debra H; Blower, Philip J; Karagiannis, Panagiotis; Lacy, Katie E; Spicer, James; Karagiannis, Sophia N; Bax, Heather J.
In: NAT COMMUN, Vol. 14, No. 1, 25.04.2023, p. 2192.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4
AU - Chauhan, Jitesh
AU - Grandits, Melanie
AU - Palhares, Lais C G F
AU - Mele, Silvia
AU - Nakamura, Mano
AU - López-Abente, Jacobo
AU - Crescioli, Silvia
AU - Laddach, Roman
AU - Romero-Clavijo, Pablo
AU - Cheung, Anthony
AU - Stavraka, Chara
AU - Chenoweth, Alicia M
AU - Sow, Heng Sheng
AU - Chiaruttini, Giulia
AU - Gilbert, Amy E
AU - Dodev, Tihomir
AU - Koers, Alexander
AU - Pellizzari, Giulia
AU - Ilieva, Kristina M
AU - Man, Francis
AU - Ali, Niwa
AU - Hobbs, Carl
AU - Lombardi, Sara
AU - Lionarons, Daniël A
AU - Gould, Hannah J
AU - Beavil, Andrew J
AU - Geh, Jenny L C
AU - MacKenzie Ross, Alastair D
AU - Healy, Ciaran
AU - Calonje, Eduardo
AU - Downward, Julian
AU - Nestle, Frank O
AU - Tsoka, Sophia
AU - Josephs, Debra H
AU - Blower, Philip J
AU - Karagiannis, Panagiotis
AU - Lacy, Katie E
AU - Spicer, James
AU - Karagiannis, Sophia N
AU - Bax, Heather J
N1 - © 2023. The Author(s).
PY - 2023/4/25
Y1 - 2023/4/25
N2 - 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 ~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.
AB - 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 ~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.
U2 - 10.1038/s41467-023-37811-3
DO - 10.1038/s41467-023-37811-3
M3 - SCORING: Journal article
C2 - 37185332
VL - 14
SP - 2192
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -