In situ photoimmunotherapy: a tumour‐directed treatment for melanoma

We report a new immunological treatment for advanced cutaneous melanoma which combines laser stimulation with topical application of a toll‐like receptor agonist. This treatment, in situ photoimmunotherapy (ISPI), provides an alternative to traditional therapies for melanoma patients with cutaneous metastases. A 6‐week cycle of ISPI is carried out on cutaneous metastases located in a designated 20 × 20 cm treatment area: 2 weeks of pretreatment with twice‐daily topical applications of imiquimod (5% cream under plastic occlusion), with a laser treatment session at week 2 and again at week 4. Topical imiquimod is continued for the entire 6‐week cycle. Two patients with late‐stage melanoma were treated with ISPI. Patient 1 had the primary tumour and local metastases on the left arm, as well as metastatic tumours in the lungs [American Joint Committee on Cancer (AJCC) stage IV]. Patient 2 had a head and neck melanoma with multiple local metastases (AJCC stage IIIC), which had failed repeated attempts at surgical resection and high‐dose radiation therapy. Patient 1 is now free of all clinically detectable tumours (including the lung metastases) >20 months after the first treatment cycle. Patient 2 has been free of any clinical evidence of the tumour for over 6 months. These two cases demonstrate that ISPI can clear local tumour and trigger beneficial systemic responses, with a side‐effect profile that compares favourably with other treatments for advanced melanoma.

[1]  F. Hodi,et al.  Melanoma of unknown primary: experience at Massachusetts General Hospital and Dana-Farber Cancer Institute , 2005, Melanoma research.

[2]  P. Lambert,et al.  Co-administration of CpG oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response. , 2004, Vaccine.

[3]  C. Cooper,et al.  CPG 7909, an Immunostimulatory TLR9 Agonist Oligodeoxynucleotide, as Adjuvant to Engerix-B® HBV Vaccine in Healthy Adults: A Double-Blind Phase I/II Study , 2004, Journal of Clinical Immunology.

[4]  S. Wagner,et al.  CpG motifs are efficient adjuvants for DNA cancer vaccines. , 2004, The Journal of investigative dermatology.

[5]  D. Persing,et al.  Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents , 2004, Expert opinion on biological therapy.

[6]  B. Pulendran Modulating vaccine responses with dendritic cells and Toll‐like receptors , 2004, Immunological reviews.

[7]  J. Thomas,et al.  Management of in‐transit metastases from cutaneous malignant melanoma , 2004, The British journal of surgery.

[8]  A. Veyre,et al.  In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases , 2004, The British journal of dermatology.

[9]  D. Golenbock,et al.  Haemophilus influenzae Type b-Outer Membrane Protein Complex Glycoconjugate Vaccine Induces Cytokine Production by Engaging Human Toll-Like Receptor 2 (TLR2) and Requires the Presence of TLR2 for Optimal Immunogenicity1 , 2004, The Journal of Immunology.

[10]  H. Kerl,et al.  Locoregional Cutaneous Metastases of Malignant Melanoma and their Management , 2004, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[11]  T. Luger,et al.  Imiquimod, pegyliertes Interferon-α-2b und Interleukin-2 in der Behandlung kutaner Melanommetastasen , 2004, Der Hautarzt.

[12]  Hong Liu,et al.  Induced antitumor immunity against DMBA‐4 metastatic mammary tumors in rats using laser immunotherapy , 2003, International journal of cancer.

[13]  A. Awada,et al.  Management of Cutaneous Locoregional Recurrences of Melanoma: A New Therapeutic Perspective with Imiquimod , 2003, Dermatology.

[14]  B. Bonnekoh,et al.  Imiquimod, a Topical Immune Response Modifier, in the Treatment of Cutaneous Metastases of Malignant Melanoma , 2002, Dermatology.

[15]  Martin F. Mihm,et al.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  G. Schuler,et al.  Topical imiquimod treatment of a cutaneous melanoma metastasis. , 2000, Journal of the American Academy of Dermatology.

[17]  Martin F. Mihm,et al.  A new American Joint Committee on Cancer staging system for cutaneous melanoma , 2000, Cancer.

[18]  Wei R. Chen,et al.  Long‐term tumor resistance induced by laser photo‐immunotherapy , 1999, International journal of cancer.

[19]  Brown Tj,et al.  Malignant melanoma: a clinical review. , 1999 .

[20]  C. Loquai,et al.  [Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases]. , 2004, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[21]  R. Nordquist,et al.  Antitumor immunity induced by laser immunotherapy and its adoptive transfer. , 2001, Cancer research.

[22]  B. Nelson,et al.  Malignant melanoma: a clinical review. , 1999, Cutis.