acyclovir and Melanoma

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Topics: Acyclovir; Adult; Aged; Antifungal Agents; Antineoplastic Agents, Alkylating; Antiviral Agents; Cyclophosphamide; Cytotoxicity, Immunologic; Female; Fluconazole; Granulocyte Colony-Stimulating Factor; Humans; Immunotherapy, Adoptive; Interferon-gamma; Interleukin-2; Lymphocyte Activation; Lymphocyte Depletion; Lymphocytes, Tumor-Infiltrating; Male; Melanoma; Middle Aged; Skin Neoplasms; Vidarabine

To describe a case of nivolumab-induced ulcerative keratitis rapidly recovering on topical steroid treatment and to determine changes in cytokine levels in the tear fluid caused by nivolumab.. We report a 34-year-old man receiving nivolumab for metastasized melanoma with severe dry eye symptoms and a persistent corneal epithelial defect. Levels of cytokine and matrix metalloproteinase in tear fluid were measured by multiplex immunoassays.. The corneal epithelial defect failed to recover for antiviral and lubrication therapy but resolved within 48 hours after topical steroid therapy was initiated. No recurrence of corneal ulceration was observed with intermittent topical steroid therapy during the remaining period of nivolumab treatment. No Sjögren disease-related autoantibodies were detected in the patient's serum. The levels of inflammatory cytokines and matrix metalloproteinases in the tear fluid were markedly elevated after nivolumab treatment.. Our observations suggest that nivolumab treatment induces a local autoimmune ocular surface disorder resulting in corneal ulceration that promptly resolves using steroid eye drops. The integrity of the corneal epithelial layer can be sustained using intermittent topical steroid therapy in patients receiving nivolumab.

Topics: Acyclovir; Adult; Antiviral Agents; Corneal Ulcer; Cytokines; Dry Eye Syndromes; Humans; Immune Checkpoint Inhibitors; Immunoassay; Male; Matrix Metalloproteinases; Melanoma; Nivolumab; Skin Neoplasms; Tears

Topics: Acyclovir; Adult; Antiviral Agents; Encephalitis, Herpes Simplex; Epilepsy, Tonic-Clonic; Humans; Male; Melanoma; Meningeal Neoplasms; Paraparesis; Quadriplegia; Ventriculostomy

Topics: Acyclovir; Aged; Antiviral Agents; Diagnosis, Differential; Head and Neck Neoplasms; Herpes Zoster; Humans; Male; Melanoma; Pruritus; Scalp Dermatoses; Skin Neoplasms

Cyclopentenylcytosine (CPE-C, 2), a pyrimidine analogue of the fermentation derived carbocyclic nucleoside neplanocin A, has been synthesized from the optically active cyclopentenylamine 3b by two synthetic routes. CPE-C demonstrates significant antitumor activity against both the sensitive and ara-C resistant lines of L1210 leukemia in vivo. Multiple long term survivors are produced in both tumor models. The compound also gives 100% growth inhibition of the solid human A549 lung and MX-1 mammary tumor xenografts grown in athymic mice. Good activity is also observed against a third human tumor xenograft model, metastatic LOX melanoma. CPE-C has significant activity against both DNA and RNA viruses in vitro. Potent activity is observed against HSV-1 (TK+ and TK-), HSV-2, vaccinia, cytomegalovirus, and varicella-zoster virus. Good activity is also found against a strain of influenza virus (Hong Kong flu), vesicular stomatitis virus, Japanese encephalitis virus, and Punta Toro virus.

Topics: 3-Deazauridine; Animals; Antineoplastic Agents; Antiviral Agents; Chemical Phenomena; Chemistry; Cytidine; DNA Viruses; Humans; Leukemia L1210; Leukemia P388; Lung Neoplasms; Mammary Neoplasms, Experimental; Melanoma; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Orthomyxoviridae; RNA Viruses; Sarcoma, Experimental; Viruses

Microencapsulation technology makes it possible to encapsulate virus infected human or animal cells in microcapsules with semipermeable membranes. These may be implanted intraperitoneally into mice which may then be treated with antiviral drugs. The implanted microcapsules may be recovered at various intervals following in vivo treatment and the effect of the drug is evaluated by assaying the virus titers inside the microcapsules. In this paper, the feasibility of this model was tested using microencapsulated human or non-human cells infected with herpes simplex virus type 1. The microcapsules were implanted in the peritoneal cavity of mice, and the effect of systematically administered acyclovir on HSV-1 replication was ascertained. We found that (a) HSV-1 can replicate in both human (A549 and FEMx) and non-human (Vero) cells after they are infected and encapsulated. (b) HSV-1 replication was inhibited by 0.005 microgram/ml to 0.08 mg/ml of acyclovir in the medium when virus producing A549 cells were encapsulated or when they were in monolayers. (c) Acyclovir (20-80 mg/kg), injected twice daily by intraperitoneal, subcutaneous or intravenous routes in mice, significantly inhibited HSV-1 production in encapsulated Vero cells implanted in the peritoneal cavity. The major advantage of this in vivo model is that it can be used to study antivirals in experimental animals in which viruses do not replicate in non-permissive animals. Toxicity, pharmacokinetic and efficacy data may be obtained. It can also be used to test drugs which require activation in vivo to be effective.

Topics: Acyclovir; Analysis of Variance; Animals; Capsules; Cell Division; Cell Survival; Diffusion Chambers, Culture; Dose-Response Relationship, Drug; Humans; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Melanoma; Mice; Permeability; Simplexvirus; Tumor Cells, Cultured; Vero Cells; Virus Replication