gammadelta T lymphocytes count is normal and expandable in peripheral blood of patients with follicular lymphoma, whereas it is decreased in tumor lymph nodes compared with inflammatory lymph nodes.

gammadelta T lymphocytes are attractive effector cells for immunotherapy. In vitro, they can be expanded and kill efficiently a variety of tumor cells. The frequency and distribution of gammadelta T lymphocytes were compared in tumor lymph nodes of 51 patients with follicular lymphoma lymph nodes (FL-LNs) and 28 patients with inflammatory lymph nodes (I-LNs).

[About a phase I gene therapy clinical trial with a full-length dystrophin gene-plasmid in Duchenne/Becker muscular dystrophy].

This is the first gene transfer trial in Duchenne/Becker patients. The aim of the study was to provide evidence on transgene expression and safety of the intramuscular administration of a plasmid containing a full-length dystrophin CDNA. Nine Duchenne/Becker patients, distributed in three cohorts of three patients, were injected into their radialis muscles either once with 200 microg (first cohort) or 600 microg (second cohort) or twice, two weeks apart, with 600 microg plasmidic DNA (third cohort).

Gene-based cancer immunotherapy and vaccines.

Extract: Cancer cells are able to escape immune detection and/or rejection by a variety of measures. Cell surface molecules, which are required for the effective policing of tissues by the immune system, are often modified, reduced or eliminated. In addition cancer cells secrete soluble molecules that inhibit the patients' ability to develop an immune response.

Phase I study of dystrophin plasmid-based gene therapy in Duchenne/Becker muscular dystrophy.

Nine patients with Duchenne or Becker muscular dystrophy were injected via the radialis muscle with a full-length human dystrophin plasmid, either once with 200 or 600 microg of DNA or twice, 2 weeks apart, with 600 microg of DNA. In the biopsies taken 3 weeks after the initial injection, the vector was detected at the injection site in all patients. Immunohistochemistry and nested reverse transcription-polymerase chain reaction indicated dystrophin expression in six of nine patients.

Gene-based vaccines and immunotherapeutics.

DNA vaccines, comprised of plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies, and cancer; plasmids encoding normal human proteins are likewise being tested as vaccines and treatments for autoimmune diseases. Examples of in vivo prophylaxis and immunotherapy, based on different types of immune responses (humoral and cellular), in a variety of disease models and under evaluation in early phase human clinical trials are presented. Viral vectors continue to show better levels of expression than those achieved by DNA plasmid vectors.

Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas.

Primary cutaneous lymphomas have been successfully treated with interferons (IFNs), counterbalancing the T-helper 2 (Th2)-skewing state. We undertook a phase 1, open-label, dose-escalating trial of repeated intratumoral administration of TG1042 in patients with advanced primary cutaneous T-cell lymphomas (CTCLs) and multilesional cutaneous B-cell lymphomas (CBCLs). TG1042 is a third-generation, nonreplicating human adenovirus vector containing a human IFN-gamma cDNA insert.

Phase I trial of antigen-specific gene therapy using a recombinant vaccinia virus encoding MUC-1 and IL-2 in MUC-1-positive patients with advanced prostate cancer.

MUC-1 is overexpressed on many tumor cells. In addition, aberrant glycosylation of MUC-1 on human tumors leads to exposure of cryptic peptide epitopes that play a role in tumor immunity. As such, it has been identified as a potential target for immunotherapy.

Therapeutic cancer vaccines.

Therapeutic vaccination against cancer-associated antigens represents an attractive option for cancer therapy in view of the comparatively low toxicity and, so far, excellent safety profile of this treatment. Nevertheless, it is now recognized that the vaccination strategies used for prophylactic vaccinations against infectious diseases cannot necessarily be used for therapeutic cancer vaccination. Cancer patients are usually immunosuppressed, and most cancer-associated antigens are self antigens.

Metastatic Breast Tumour Regression Following Treatment by a Gene-Modified Vaccinia Virus Expressing MUC1 and IL-2.

MUC1 is expressed by glandular epithelial cells. It is overexpressed in the majority of breast tumours, making it a potential target for immune therapy. The objectives of the present study were to evaluate the anti-tumour activity and tolerance of repeated administration of TG1031 (an attenuated recombinant vaccinia virus containing sequences coding for human MUC1 and the immune stimulatory cytokine IL-2) in patients with MUC1-positive metastatic breast cancer.

Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer.

Background: The MUC1 protein is a highly glycosylated mucin normally found at the apical surface of mucin-secreting epithelial cells in many types of tissues. MUC1 is expressed, but heavily underglycosylated, in different human tumors. TG4010 is a viral suspension of a recombinant vaccinia vector (MVA) containing DNA sequences coding for the human MUC1 antigen and interleukin-2 (IL-2).

Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part I: rationale.

Since the identification of abnormalities in the dystrophin gene as primary cause of Duchenne muscular dystrophy, gene therapy has been seen as an obvious option among various approaches to treat the disease. It is also considered to be especially challenging, as in this context, one must achieve massive transfer of the gene with a sustained lifelong correction of the muscle phenotype. Our goal is to allow large scale transfection of skeletal muscle fibers of Duchenne muscular dystrophy patients with the full-length 11-kb human dystrophin cDNA.

Current protocol of a research phase I clinical trial of full-length dystrophin plasmid DNA in Duchenne/Becker muscular dystrophies. Part II: clinical protocol.

A phase I open clinical study on gene therapy in Duchenne and Becker muscular dystrophy, without direct individual benefit for the patient, is being performed at the Pitié-Salpêtrière Hospital, Paris. The aims of this project are: (a) to determine the tolerance and the safety of the intramuscular administration of dystrophin cDNA and (b) to study the quality of the gene transfer in vivo in human patients affected by Duchenne and Becker muscular dystrophy. This clinical trial is conducted sequentially and includes three cohorts of three patients each.

Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: phase II randomized study comparing two dose levels.

Background: Systemic IL-2 has shown some activity in metastatic melanoma, but its use is severely limited by toxicity. TG2001 is a product in which the human IL-2 cDNA was incorporated into the genome of Vero cells, a monkey fibroblast cell line. The goal of this intratumorally applied therapy was to create an antitumor immune response stimulated by xeno-antigens and local production of IL-2 in the close vicinity of tumor-specific antigens.