Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma

Xinyi Chen; Shabana Habib; Madalina Alexandru; Jitesh Chauhan; Theodore Evan; Joanna M Troka; Avigail Rahimi; Benjamina Esapa; Thomas J Tull; Wen Zhe Ng; Amanda Fitzpatrick; Yin Wu; Jenny L C Geh; Hawys Lloyd-Hughes; Lais C G F Palhares; Rebecca Adams; Heather J Bax; Sean Whittaker; Joanna Jacków-Malinowska; Sophia N Karagiannis

doi:10.3390/cancers16193260

Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma

Xinyi Chen, Shabana Habib, Madalina Alexandru, Jitesh Chauhan, Theodore Evan, Joanna M Troka, Avigail Rahimi, Benjamina Esapa, Thomas J Tull, Wen Zhe Ng, Amanda Fitzpatrick, Yin Wu, Jenny L C Geh, Hawys Lloyd-Hughes, Lais C G F Palhares, Rebecca Adams, Heather J Bax, Sean Whittaker, Joanna Jacków-Malinowska, Sophia N Karagiannis

Research output: Contribution to journal › Review article › peer-review

Abstract

Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody-drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.

Original language	English
Article number	3260
Journal	Cancers
Volume	16
Issue number	19
DOIs	https://doi.org/10.3390/cancers16193260
Publication status	Published - 25 Sept 2024

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Chen, X., Habib, S., Alexandru, M., Chauhan, J., Evan, T., Troka, J. M., Rahimi, A., Esapa, B., Tull, T. J., Ng, W. Z., Fitzpatrick, A., Wu, Y., Geh, J. L. C., Lloyd-Hughes, H., Palhares, L. C. G. F., Adams, R., Bax, H. J., Whittaker, S., Jacków-Malinowska, J., & Karagiannis, S. N. (2024). Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma. Cancers, 16(19), Article 3260. https://doi.org/10.3390/cancers16193260

@article{534d87c92f4b4fe29a62b4a2aa2a989c,

title = "Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma",

abstract = "Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody-drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.",

author = "Xinyi Chen and Shabana Habib and Madalina Alexandru and Jitesh Chauhan and Theodore Evan and Troka, {Joanna M} and Avigail Rahimi and Benjamina Esapa and Tull, {Thomas J} and Ng, {Wen Zhe} and Amanda Fitzpatrick and Yin Wu and Geh, {Jenny L C} and Hawys Lloyd-Hughes and Palhares, {Lais C G F} and Rebecca Adams and Bax, {Heather J} and Sean Whittaker and Joanna Jack{\'o}w-Malinowska and Karagiannis, {Sophia N}",

year = "2024",

month = sep,

day = "25",

doi = "10.3390/cancers16193260",

language = "English",

volume = "16",

journal = "Cancers",

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Chen, X, Habib, S, Alexandru, M , Chauhan, J , Evan, T, Troka, JM, Rahimi, A, Esapa, B , Tull, TJ, Ng, WZ, Fitzpatrick, A , Wu, Y, Geh, JLC, Lloyd-Hughes, H, Palhares, LCGF, Adams, R , Bax, HJ , Whittaker, S, Jacków-Malinowska, J & Karagiannis, SN 2024, 'Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma', Cancers, vol. 16, no. 19, 3260. https://doi.org/10.3390/cancers16193260

TY - JOUR

T1 - Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma

AU - Chen, Xinyi

AU - Habib, Shabana

AU - Alexandru, Madalina

AU - Chauhan, Jitesh

AU - Evan, Theodore

AU - Troka, Joanna M

AU - Rahimi, Avigail

AU - Esapa, Benjamina

AU - Tull, Thomas J

AU - Ng, Wen Zhe

AU - Fitzpatrick, Amanda

AU - Wu, Yin

AU - Geh, Jenny L C

AU - Lloyd-Hughes, Hawys

AU - Palhares, Lais C G F

AU - Adams, Rebecca

AU - Bax, Heather J

AU - Whittaker, Sean

AU - Jacków-Malinowska, Joanna

AU - Karagiannis, Sophia N

PY - 2024/9/25

Y1 - 2024/9/25

N2 - Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody-drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.

AB - Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody-drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.

U2 - 10.3390/cancers16193260

DO - 10.3390/cancers16193260

M3 - Review article

C2 - 39409881

SN - 2072-6694

VL - 16

JO - Cancers

JF - Cancers

IS - 19

M1 - 3260

ER -

Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma

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