pep005 and Lung-Neoplasms

Ingenol mebutate (IM) has recently been approved for the topical treatment of actinic keratoses. It appears to have a dual mechanism of action: rapid necrosis after gel application and a subsequent immune-mediated response, which targets any residual dysplastic epidermal cells. We report the successful treatment of a woman, who had been relapsing into Bowen's disease (BD) on her right forefinger for 8 years. During her clinical history, she had received an allogeneic, HLA-identical stem cell transplant for myeloproliferative syndrome with a JAK2V617F mutation and lobectomy of the pulmonary right lower lobe for adenocarcinoma. We used dermoscopy to monitor the therapeutic response of BD. We discuss IM gel as a possible therapeutic option for BD.

Topics: Adenocarcinoma; Administration, Cutaneous; Aged; Antineoplastic Agents; Bowen's Disease; Dermoscopy; Diterpenes; Female; Fingers; Gels; Humans; Lung Neoplasms; Myeloproliferative Disorders; Neoplasm Recurrence, Local; Pneumonectomy; Skin Neoplasms; Stem Cell Transplantation

Ingenol-3-angelate is a new local chemotherapeutic agent in clinical trails that induces primary necrosis of tumour cells and transient local inflammation. Here we show that cure of subcutaneous tumours with ingenol-3-angelate (PEP005) resulted in the generation of anti-cancer CD8 T cells that could regress metastases. Furthermore, PEP005-mediated cure synergized with several CD8 T cell-based immunotherapies to regress further distant metastases. PEP005 was shown to have adjuvant properties, being able to upregulate CD80 and CD86 expression on dendritic cells in vivo, and to promote CD8 T cell induction when co-delivered with a protein antigen. PEP005 thus emerges as a unique local chemotherapeutic immunostimulatory debulking agent that could be used in conjunction with immunotherapies to promote regression of metastases.

Topics: Adjuvants, Immunologic; Animals; Cancer Vaccines; Carcinoma, Lewis Lung; Cell Culture Techniques; Chickens; Colonic Neoplasms; Dendritic Cells; Diterpenes; Female; Humans; Immunization; Lung Neoplasms; Melanoma, Experimental; Mice; Neoplasm Transplantation; Neoplasms; T-Lymphocytes