Abstract
Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1-PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 511-519 |
| Number of pages | 9 |
| Journal | Archives of Dermatological Research |
| Volume | 306 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- BRAF
- Immunotherapy
- Ipilimumab
- Melanoma
- MK-3475
- Nivolumab
- PD-1
- PD-L1
- Programmed cell death receptor 1
ASJC Scopus subject areas
- Dermatology
Cite this
Targeting the PD-1 pathway : A promising future for the treatment of melanoma. / Mamalis, Andrew; Garcha, Manveer; Jagdeo, Jared.
In: Archives of Dermatological Research, Vol. 306, No. 6, 2014, p. 511-519.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting the PD-1 pathway
T2 - A promising future for the treatment of melanoma
AU - Mamalis, Andrew
AU - Garcha, Manveer
AU - Jagdeo, Jared
PY - 2014
Y1 - 2014
N2 - Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1-PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.
AB - Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1-PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.
KW - BRAF
KW - Immunotherapy
KW - Ipilimumab
KW - Melanoma
KW - MK-3475
KW - Nivolumab
KW - PD-1
KW - PD-L1
KW - Programmed cell death receptor 1
UR - http://www.scopus.com/inward/record.url?scp=84904751102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904751102&partnerID=8YFLogxK
U2 - 10.1007/s00403-014-1457-7
DO - 10.1007/s00403-014-1457-7
M3 - Article
C2 - 24615548
AN - SCOPUS:84904751102
VL - 306
SP - 511
EP - 519
JO - Archives of Dermatological Research
JF - Archives of Dermatological Research
SN - 0340-3696
IS - 6
ER -