Skin Reactions in a Subset of Patients With Stage IV Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen 4 Monoclonal Antibody as a Single Agent

Jaber, Samer H.; Cowen, Edward W.; Haworth, Leah; Booher, Susan; Berman, David M.; Rosenberg, Steven A.; Hwang, Samuel T

doi:10.1001/archderm.142.2.166

Cited by 107 publications

(90 citation statements)

References 23 publications

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“…Importantly, CTLA-4 blockade also completely reversed the CD4 + T-cell deficit and normalized the ratio of T Regs in tumor-bearing mice displaying the same deficiencies found in humans with MGs [62]. While enhancing cross-priming or eliminating the suppression of endogenous antitumor immune responses through the elimination of regulatory T-cells [44,61] or blocking of CTLA-4 signaling [62], for example, may be effective strategies, they will run the risk of inducing uncontrollable autoimmunity [63][64][65][66].…”

Section: Immunosuppression In Patients With Malignant Gliomasmentioning

confidence: 95%

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

Sampson

Archer

Mitchell

et al. 2008

Seminars in Immunology

153

131

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Conventional therapies for malignant gliomas (MGs) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by non-specific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells.The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in MGs and other neoplasms. This mutation encodes a constitutively active tyrosine kinase that enhances tumorgenicity and migration and confers radiation and chemotherapeutic resistance. This in-frame deletion mutation splits a codon resulting in the creation of a novel glycine at the fusion junction between normally distant parts of the molecule and producing a sequence rearrangement which creates a tumor-specific epitope for cellular or humoral immunotherapy in patients with MGs.We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction is an efficacious immunotherapy in syngeneic murine models, but patients with MGs have a profound immunosuppression that may inhibit the ability of antigen presenting cells (APCs), even those generated ex vivo, to induce EGFRvIII-specific immune responses. In this report, we summarize our results in humans targeting this mutation in two consecutive and one multi-institutional Phase II immunotherapy trials. These trials demonstrated that vaccines targeting EGFRvIII are capable of inducing potent T-and B-cell immunity in these patients, and an unexpectedly long survival time. Most importantly, vaccines targeting EGFRvIII were universally successful at eliminating tumor cells expressing the targeted antigen without any evidence of symptomatic collateral toxicity.These studies establish the tumor-specific EGFRvIII mutation as a novel target for humoral-and cell-mediated immunotherapy in a variety of cancers. The recurrence of EGFRvIII-negative tumors in our patients, however, highlights the need for targeting a broader repertoire of tumor-specific antigens. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , and patients with recurrent tumors usually survive <20 weeks [7]. Moreover, the non-specific nature of conventional therapy for brain tumors often results in incapacitating damage to surrounding normal brain and systemic tissues [8]. Thus, in order to be more effective, therapeutic strategies will have to precisely target tumor cells while minimizing collateral damage to neighboring eloquent cerebral cortex. The rationale for employing the immune system to target brain tumors is based on the p...

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Section: Immunosuppression In Patients With Malignant Gliomasmentioning

confidence: 95%

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

Sampson

Archer

Mitchell

et al. 2008

Seminars in Immunology

153

131

View full text Add to dashboard Cite

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“…Additionally, anti-CTLA-4 antibodies may stimulate an immune response against melanocytes. The development of vitiligo in a subset of patients and the identification of Melan-A-specific CD8 + T lymphocytes near apoptotic melanocytes in biopsy specimens supports this theory [2,6].…”

Section: Discussionmentioning

confidence: 75%

“…Epidermal spongiosis and, rarely, dyskeratosis are also observed. Other skin findings include alopecia of the scalp, eyebrows, face, pubic region, and trunk as well as a photosensitive eruption [6]. Additionally, anti-CTLA-4 antibodies may stimulate an immune response against melanocytes.…”

Section: Discussionmentioning

confidence: 99%

A case of Stevens–Johnson syndrome in a patient on ipilimumab

Pathria

Mundi²,

Trufant³

2016

IJCRI

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International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations.

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“…Patient 2 experienced both vitiligo and alopecia universalis. The latter has been reported only once previously with ipilimumab therapy 24 .…”

Section: Discussionmentioning

confidence: 89%

Immune Toxicities and Long Remission Duration after Ipilimumab Therapy for Metastatic Melanoma: Two Illustrative Cases

Assi

Wilson

2013

Current Oncology

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New antitumour immunotherapy strategies for stage IV metastatic melanoma include ipilimumab, a monoclonal antibody against CTLA-4. Patterns of response with cancer immunotherapy differ from those with cytotoxic chemotherapy. We present two cases of long-duration immune-related responses with ipilimumab in a phase II trial. A 66-year-old woman with multiple lung metastases from a scalp primary melanoma received 4 doses of ipilimumab with mixed clinical response. However, after the first maintenance dose, she developed severe ileitis and colitis that responded to steroid therapy. Four months later, she had surgery and radiotherapy for a single brain metastasis. Radiologically, stable disease continued for 36 months after the last ipilimumab dose, and partial response for 5 years after ipilimumab start. A 54-year-old man with cervical lymph node and pulmonary metastases from a scalp primary melanoma received three induction doses of ipilimumab. He developed alopecia universalis and widespread vitiligo, and he discontinued treatment because of hypophysitis. Maintenance ipilimumab was started after a 6-month drug-free interval, with no further adverse events over 15 cycles. At week 12, computed tomography imaging showed no lung metastases and partial response in a supraclavicular lymph node, which was positive on positron-emission tomography. Five years after starting ipilimumab, the supraclavicular lymph node was calcified, and the patient was off steroid therapy and asymptomatic. The foregoing patients demonstrate long responses with ipilimumab (in association with delayed severe colitis in one case, and a constellation of immune events, including alopecia universalis in another). Re-treatment with ipilimumab may be possible even after significant immune adverse events.

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Skin Reactions in a Subset of Patients With Stage IV Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen 4 Monoclonal Antibody as a Single Agent

Cited by 107 publications

References 23 publications

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma

A case of Stevens–Johnson syndrome in a patient on ipilimumab

Immune Toxicities and Long Remission Duration after Ipilimumab Therapy for Metastatic Melanoma: Two Illustrative Cases

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