ABSTRACT
BACKGROUND: This study was conducted to test the efficacy of a new cancer vaccine, composed of dendritic cells (DCs) pulsed with an interleukin-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) in a CC-36 murine colon adenocarcinoma model. MATERIALS AND METHODS: CC-36 tumor cells were injected subcutaneously into the left flank of four- to six-week old male BALB/c mice. The mice were divided into three groups, each of which received one of the following treatments: (1) DCs pulsed with the IL-2 gene-encoded vaccinia oncolysate (DC-IL-2VCO), (2) DCs pulsed with the tumor oncolysate alone (DC-CO), or (3) no treatment (control). Tumor incidence was measured, and survival rates were compared using a paired Student's t-test. Cytolytic T cell activity was measured in peripheral blood lymphocytes (PBL) and splenic lymphocytes using a (51)Cr-release assay. Lastly, mice were depleted of either CD4+ or CD8+ lymphocytes prior to receiving the vaccine to test the mechanism of tumor immunity in these mice. RESULTS: Mice treated with DC-IL-2VCO demonstrated decreased tumor burden, increased survival, and greater cytolytic activity compared with control mice and mice receiving DC-CO. In addition, mice depleted of CD8+ T cells prior to immunization with IL-2VV + DC-IL-2VCO had a significant increase in the incidence of tumor, similar to the untreated control mice. CONCLUSIONS: DCs pulsed with an IL-2 gene-encoded vaccinia virus tumor oncolysate (DC-IL-2VCO) produced safe and effective immune responses in a murine CC-36 colon adenocarcinoma model. This vaccine (DC-MelVac; Patent no. 11221/5) has the potential to treat humans with cancer, and has received FDA approval for use in Phase I clinical trials.
Subject(s)
Adenocarcinoma/pathology , Cancer Vaccines/pharmacology , Colonic Neoplasms/pathology , Dendritic Cells/metabolism , Interleukin-2/metabolism , Adenocarcinoma/epidemiology , Adenocarcinoma/immunology , Adenocarcinoma/mortality , Animals , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Cell Line , Chlorocebus aethiops , Colonic Neoplasms/epidemiology , Colonic Neoplasms/immunology , Colonic Neoplasms/mortality , Dendritic Cells/cytology , Gene Transfer Techniques , Genetic Vectors , Humans , Incidence , Interleukin-2/genetics , Male , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Spleen/cytology , Survival Analysis , T-Lymphocytes, Cytotoxic/pathology , Tumor Burden , Vaccinia virus/geneticsABSTRACT
Dendritic cells (DCs) possess the unique abilities to initiate a primary immune response and to present antigens to naïve T lymphocytes. Recently, there has been a rapidly growing interest in the use of DCs in active specific immunotherapy (ASI) for the treatment of patients with cancer. In the present study, we determined the ability of DCs to express Melanoma-Associated Antigens (MAAs) from a polyvalent Melanoma Vaccine (DC-MelVac; Patent #11221/5) developed in our facility. The vaccine consists of a recombinant IL-2 gene-encoded vaccinia melanoma oncolysate (rIL-2VMO) derived from an established human melanoma cell line. Our results show that r-IL2VMO-pulsed DCs express MAAs presented by the Mel-2 melanoma cell line oncolysate used in this study. We believe that these promising results will prove useful as an active specific immunotherapeutic agent for patients with Stage III melanoma.
Subject(s)
Antigens, Neoplasm/immunology , Dendritic Cells/immunology , Interleukin-2/genetics , Melanoma/immunology , Neoplasm Proteins/immunology , Antigen-Presenting Cells/immunology , Cancer Vaccines , Dendritic Cells/ultrastructure , Humans , Recombinant Proteins/immunology , Reference Values , T-Lymphocytes/immunologyABSTRACT
Melanoma continues to be one of the most difficult to treat of all solid tumors. Many new advances have been made in the surgical management of melanoma, including new guidelines for margins of excision, as well as sentinel node biopsy for the diagnosis of lymph node micrometastases. The search continues for an effective adjuvant melanoma treatment that can prevent local and distant recurrences. Melanoma is one of the most immunogenic of all tumors, and several clinical trials testing the immunotherapy of melanoma have been conducted, including trials in interferon, interleukin-2, and melanoma vaccines. Here we discuss many of the recent clinical trials in the surgical management of melanoma, in addition to the advances that have been made in the field of immunotherapy. A new second-generation melanoma vaccine, DC-MelVac (patent # 11221/5), has recently been granted FDA approval for Phase I clinical trials and will be introduced in this review.
Subject(s)
Immunotherapy/methods , Melanoma/immunology , Melanoma/therapy , Cancer Vaccines , Clinical Trials as Topic , Humans , Interferon-alpha/immunology , Interleukin-2/immunology , Lymphatic Metastasis , Sentinel Lymph Node Biopsy , Skin Neoplasms/immunology , Skin Neoplasms/therapyABSTRACT
Gastroparesis is a debilitating condition that affects a significant number of diabetic patients. Some of these patients have end-stage renal disease and are in need of kidney transplant. Symptoms of gastroparesis include: early satiety, pyrosis, epigastric pain, nausea and vomiting, which may lead to caloric and electrolyte deficiencies as well as significant weight loss. A viable option for diabetic gastroparesis patients who fail first line treatments consisting of dietary changes and gastric prokinetic medications is gastric electrical stimulator (GES) implantation. We present a 41-yr-old man and 35-yr-old woman with diabetic gastroparesis, who were initially deemed unacceptable candidates for renal transplantation because of marked malnourishment and a concern that they would not be able to tolerate immunosuppressant medications. In less than two yr following GES implantation, each patient underwent a successful kidney transplant.
