Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma.

Background: The growth and recurrence of several cancers appear to be driven by a population of cancer stem cells (CSCs). Glioblastoma, the most common primary brain tumor, is invariably fatal, with a median survival of approximately 1 year. Although experimental data have suggested the importance of CSCs, few data exist regarding the potential relevance and importance of these cells in a clinical setting.

Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001.

Understanding the basis of a successful clinical response after treatment with therapeutic cancer vaccines is essential for the development of more efficacious therapy. After vaccination with the single telomerase (hTERT) 16-mer peptide, GV1001, some patients experienced clinical responses and long-term survival. This study reports in-depth immunological analysis of the T-cell response against telomerase (hTERT) in clinically responding patients compared with clinical non-responders following vaccination with the single hTERT 16-mer peptide, GV1001.

Vaccination of patients with cutaneous melanoma with telomerase-specific peptides.

Purpose: A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611-626) and p540 (hTERT: 540-548) using granulocyte-macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma.

Experimental Design: Ten patients with melanoma stages UICC IIb-IV were vaccinated 8 times intradermally with either 60 or 300 nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300 nmole GV1001 in combination with tuberculin PPD23 injections.

hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes.

Immunotherapy targeting the hTERT subunit of telomerase has been shown to induce robust immune responses in cancer patients after vaccination with single hTERT peptides. Vaccination with dendritic cells (DCs) transfected with hTERT mRNA has the potential to induce strong immune responses to multiple hTERT epitopes and is therefore an attractive approach to more potent immunotherapy. Blood samples from such patients provide an opportunity for identification of new, in vivo processed T-cell epitopes that may be clinically relevant.

Transiently redirected T cells for adoptive transfer.

Background Aims: T cells can be redirected to reject cancer by retroviral transduction with a chimeric antigen receptor (CAR) or by administration of a bispecific T cell engager (BiTE). We demonstrate that transfection of T cells with messenger (m) RNA coding for CAR is an alternative strategy.

Methods: We describe the pre-clinical evaluation of a method based on transient modification of expanded T cells with a CD19 CAR directed against B-cell malignancies.

Non-MHC-dependent redirected T cells against tumor cells.

Adoptive transfer of T cells with restricted tumor specificity provides a promising approach to immunotherapy of cancers. However, the isolation of autologous cytotoxic T cells that recognize tumor-associated antigens is time consuming and fails in many instances. Alternatively, gene modification with tumor antigen-specific T-cell receptors (TCR) or chimeric antigen receptors (CARs) can be used to redirect the specificity of large numbers of immune cells toward the malignant cells.

Ex vivo expansion protocol for human tumor specific T cells for adoptive T cell therapy.

Adoptive T cell therapy is a promising treatment strategy for patients with different types of cancer. The methods used for generation of high numbers of tumor specific T cells usually require long-term ex vivo culture, which frequently lead to generation of terminally differentiated effector cells, demonstrating low persistence in vivo. Therefore, optimization of protocols for generation of T cells for adoptive cell therapy is warranted.

Survey of permethrin and malathion resistance in human head lice populations from Denmark.

Head lice, Pediculis capitis De Geer, populations were investigated for permethrin and malathion resistance after initial establishment of a discriminating dose of topical application bioassay with body lice, Pediculus humanus L. For both insecticides, approximately 2 times the lethal dose (LD)95 at 4 h was selected, 2 ng of permethrin and 100 ng of malathion per head louse, respectively. Head lice were collected from heads of infested children in Denmark at 33 primary schools, one kindergarten, and seven boarding schools.