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Adoptive T-cell Transfer Therapy And Oncogene-Targeted Therapy For Melanoma: The Search For Synergy

M. L. Kwong, B. Neyns, J. Yang
Published 2013 · Medicine

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The clinical strengths of immunotherapy and small-molecule inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway appear to be largely complementary for the treatment of advanced melanoma. In current practice, most patients with BRAF V600 mutant melanomas will see both modalities. Several in vitro and in vivo studies suggest that combining immunotherapy with MAPK inhibition may have synergistic effects. First, mouse models show that adoptive cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by vemurafenib could provide a vaccine-like stimulus to adoptively transferred T cells. Second, both in mice and in early clinical trials, melanoma metastases treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third, MAPK inhibition upregulates the expression of some melanoma antigens and, therefore, may enhance T-cell recognition of vemurafenib-treated melanomas. Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally, some investigators have found that an optimal antitumor effect from MAPK inhibition is dependent on an intact host immune response. Currently, the Surgery Branch of the National Cancer Institute has initiated a phase II trial combining the BRAF inhibitor vemurafenib with ACT using tumor-infiltrating lymphocytes in patients with BRAF-mutant tumors to investigate the safety and efficacy of this combination. The proposed mechanisms for synergy between these two modalities can be complex, and their optimal combination may require testing a variety of sequences and schedules. Clin Cancer Res; 19(19); 5292–9. ©2013 AACR.
This paper references
10.1158/1078-0432.CCR-11-1823
CTLA-4 Blockade with Ipilimumab: Long-term Follow-up of 177 Patients with Metastatic Melanoma
P. A. Prieto (2012)
10.1200/JCO.2005.00.240
Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma.
M. Dudley (2005)
10.1158/1078-0432.CCR-12-1630
BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma
D. Frederick (2013)
10.1084/jem.20030590
Tumor Regression and Autoimmunity after Reversal of a Functionally Tolerant State of Self-reactive CD8+ T Cells
W. Overwijk (2003)
Combining T Cells and Vemurafenib www.aacrjournals.org Clin Cancer Res
(2013)
10.1200/JCO.2008.16.5449
Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens.
M. Dudley (2008)
10.1158/0008-5472.CAN-11-2837
BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy.
R. Koya (2012)
of Potential Conflicts of Interest No potential conflicts of interest were disclosed
American Association for Cancer Research. clincancerres.aacrjournals.org Downloaded from
(2013)
10.1158/1078-0432.CCR-10-0041
Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
M. Besser (2010)
10.1158/1078-0432.CCR-13-0143
CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients
P. Ott (2013)
10.1158/1078-0432.CCR-11-2479
Selective BRAF Inhibitors Induce Marked T-cell Infiltration into Human Metastatic Melanoma
J. Wilmott (2011)
10.1016/S0140-6736(12)60868-X
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
A. Hauschild (2012)
10.4161/onci.20226
Selective BRAF inhibition decreases tumor-resident lymphocyte frequencies in a mouse model of human melanoma
Anna I. Hooijkaas (2012)
10.1158/1078-0432.CCR-12-2731
The Activation of MAPK in Melanoma Cells Resistant to BRAF Inhibition Promotes PD-L1 Expression That Is Reversible by MEK and PI3K Inhibition
X. Jiang (2012)
10.4161/onci.22890
Vemurafenib enhances MHC induction in BRAFV600E homozygous melanoma cells
B. Sapkota (2013)
10.1200/JCO.1999.17.7.2105
High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993.
M. Atkins (1999)
10.1371/journal.pone.0047520
Pan-Bcl-2 Inhibitor AT-101 Enhances Tumor Cell Killing by EGFR Targeted T Cells
A. Thakur (2012)
10.1038/nri2545
Immunogenic and tolerogenic cell death
D. Green (2009)
10.1158/1078-0432.CCR-12-1626
BRAF Inhibition Increases Tumor Infiltration by T cells and Enhances the Antitumor Activity of Adoptive Immunotherapy in Mice
C. Liu (2012)
10.1056/NEJMoa1210093
Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations.
K. Flaherty (2012)
10.1158/1078-0432.CCR-13-0142
Navigating the Therapeutic Complexity of PI3K Pathway Inhibition in Melanoma
L. Kwong (2013)
10.1158/1541-7786.MCR-06-0077
Role of the Mitogen-Activated Protein Kinase Signaling Pathway in the Regulation of Human Melanocytic Antigen Expression
M. Kono (2006)
10.1158/1078-0432.CCR-11-0116
Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy
S. Rosenberg (2011)
10.1038/jid.2013.6
Vemurafenib induces senescence features in melanoma cells.
S. Haferkamp (2013)
10.1056/NEJMoa1112302
Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib.
J. Sosman (2012)
10.1056/NEJMoa1103782
Improved survival with vemurafenib in melanoma with BRAF V600E mutation.
P. Chapman (2011)
10.1158/1538-7445.AM2012-3928
Abstract 3928: Inhibition of the ubiquitin proteasome system differentially regulates glucocorticoid receptor-mediated transcriptional processes
K. R. Wiggins (2012)
10.1158/1078-0432.CCR-13-0259
The Cell-Cycle Regulator CDK4: An Emerging Therapeutic Target in Melanoma
K. Sheppard (2013)
10.1200/JCO.2012.43.5966
Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor.
K. Kim (2013)
10.1056/NEJMoa1203421
Improved survival with MEK inhibition in BRAF-mutated melanoma.
K. Flaherty (2012)
10.1158/0008-5472.CAN-10-0118
Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function.
A. Boni (2010)
10.1158/1078-0432.CCR-12-1632
Oncogenic BRAF(V600E) Promotes Stromal Cell-Mediated Immunosuppression Via Induction of Interleukin-1 in Melanoma
J. Khalili (2012)



This paper is referenced by
Immune Response Regulation has Thera- peutic Potential in the Treatment of Cancer
Maria Carolina Festa (2015)
10.4172/2155-9899.1000398
Cancer Specific CTL Expansion with ZYX Bioreactor
Yongxin Zhang (2016)
10.1158/1078-0432.CCR-13-2151
The Intersection of Immune-Directed and Molecularly Targeted Therapy in Advanced Melanoma: Where We Have Been, Are, and Will Be
R. Sullivan (2013)
The Therapeutic Role of NK Cells in DC Immunotherapy
F. Caldwell (2013)
Inhibition of cancer cell immune evasion by combined application of cytotoxic T-lymphocytes and natural killer cells
Y. Zhang (2018)
10.1158/1078-0432.CCR-16-0906
A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma
Drew C Deniger (2016)
Adaptive Modulation of MHC Class I Expression and Immune Evasion to Cytotoxic Immunocytes in Cancer Cells
Yongxin Zhang (2017)
10.15252/emmm.201505774
VEGF blockade enhances the antitumor effect of BRAFV 600E inhibition
Valentina Comunanza (2017)
10.1007/S40314-015-0241-4
Dynamic analysis of an antitumor model and investigation of the therapeutic effects for different treatment regimens
Liuyong Pang (2017)
10.5772/59360
Emerging Drug Combination Approaches in Melanoma Therapy
J. Wang (2015)
10.1158/2326-6066.CIR-14-0218
Cytotoxic T-cell Cytokines Put Cancer Under Arrest
S. Riddell (2014)
10.1111/bjh.13889
Chimeric Antigen Receptor (CAR) therapy for multiple myeloma
D. Atanackovic (2016)
10.7150/thno.50333
From biomarkers to therapeutic targets: the promise of PD-L1 in thyroid autoimmunity and cancer
Grégoire D’andrea (2021)
10.1158/1078-0432.CCR-13-0142
Navigating the Therapeutic Complexity of PI3K Pathway Inhibition in Melanoma
L. Kwong (2013)
10.21007/ETD.CGHS.2015.0341
Overcoming Acquired Resistance to BRAF Inhibitors by Novel Synergistic Drug Combination and Discovery of Novel Smac Mimetics as Selective Survivin Inhibitors
Jin He Wang (2015)
10.1016/j.canlet.2014.08.006
AAV-sBTLA facilitates HSP70 vaccine-triggered prophylactic antitumor immunity against a murine melanoma pulmonary metastasis model in vivo.
L. Han (2014)
Chapter 8 Emerging Drug Combination Approaches in Melanoma Therapy
J. Wang (2018)
10.1097/CMR.0000000000000203
Type I-polarized BRAF-pulsed dendritic cells induce antigen-specific CD8+ T cells that impact BRAF-mutant murine melanoma
Jessica A. Cintolo (2016)
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