Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Vaccines

vaccination with autologous dendritic cells matured with standard cytokine cocktail and electroporated with mRNA encoding tumor associated antigens

vaccination with autologous TLR-ligand matured dendritic cells electroporated with mRNA encoding tumor associated antigens

Autologous monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase and matured with either cytokines or TLR ligands. Dendritic cells are vaccinated intradermal/intravenously 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations.

autologous dendritic cell vaccination

C.J.A. Punt, prof.dr.

Objectives:

This is an exploratory study, consisting of two parts. In part I a dose escalation is performed and the primary objective is the safety of different doses of TLR-dendritic cell (TLR-DC). In part II TLR-DC vaccination will be compared with cytokine-matured DC vaccination and the primary objective of this part is the immunological response to TLR-DC vaccination, with toxicity and clinical efficacy being secondary objectives. These studies will provide important data on the safety and immunological effects of TLR-matured DC.

Study design:

This study is an open label prospective exploratory intervention study.

Study population:

The investigators' study population consists of HLA-A2.1 positive melanoma patients, with proven expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is planned or performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included.

1. Rationale

   Immunotherapy applying ex vivo generated and tumor-antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Thus far it remains unclear why some patients respond and others not, but there is a general consensus that the current protocols applied to generate DC may not result in the induction of optimal Th1 responses. We and others have demonstrated that DC maturation is one of the crucial factors, not only for effective DC migration but also to induce effective anti-tumor immune responses in cancer patients. Currently, the "golden standard" used to mature DC consists of a cocktail of pro-inflammatory cytokines (IL-1beta, IL-6, TNFalpha) and prostaglandin E2 (PGE2). Recent mouse data demonstrated, however, that maturation of DC by solely pro-inflammatory cytokines yielded DC that supported T cell clonal expansion, but failed to efficiently direct effector T cell differentiation. Interestingly, DC matured in the presence of Toll like receptor (TLR) ligands were able to induce full T cell effector function and unleashed more potent immune responses. We recently identified vaccines against infectious diseases that contain TLR ligands and are capable of inducing DC maturation. This knowledge provides a new application for these clinical applicable agents: clinical grade DC stimulators. A clinical grade DC maturation protocol is developed in which TLR ligands (preventive vaccines) and PGE2 are combined which resulted in the generation of mature DC that secrete high levels of the key cytokine IL-12. Moreover, these TLR-ligand matured DC induced T cells secreting at least 20-fold higher levels of the effector cytokines IFNalpha and TNFalpha as compared to DC matured in the absence of TLR ligands. In conclusion, these in vitro data demonstrate that TLR-ligand matured DC are promising candidates to improve immunological and clinical responses in cancer immunotherapy.
2. Objectives

   This is an exploratory study, consisting of two parts. In part I a dose escalation is performed and the primary objective is the safety of different doses of TLR-DC. In part II TLR-DC vaccination will be compared with cytokine-matured DC vaccination and the primary objective of this part is the immunological response to TLR-DC vaccination, with toxicity and clinical efficacy being secondary objectives. These studies will provide important data on the safety and immunological effects of TLR-matured DC.
3. Study design

   This study is an open label prospective exploratory intervention study.
4. Study population

   Our study population consists of HLA-A2.1 positive melanoma patients, with proven expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is planned or performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included.
5. Main study endpoints

The primary objectives of the study are to investigate the toxicity of TLR-DC by dose escalation of DC numbers in part I, and to investigate immunological responses upon TLR-DC vaccination in part II of the study.

Immunological responses are:

1. The migratory capacity of the TLR-ligand matured DC in vivo.
2. The activation of immune cells in vivo.
3. The immunological response induced with TLR-ligand matured DC loaded with mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase).

Safety and clinical efficacy are secondary objectives.

Toll-like Receptor (TLR) Ligand Matured Dendritic Cell Vaccination in Melanoma Patients

TLR Ligand Matured Dendritic Cell Vaccination in Melanoma Patients: the Key Towards a More Potent Immune Induction?

in terms of local injection site reaction, flu-like symptoms, or otherwise related to vaccination, scored according to CTC version 3.0

time to progression from date of start (apheresis) will be recorded

Radboud University Medical Center

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Diseases and Abnormalities at or Before Birth

Carcinoma

Breast Neoplasms

Colorectal Neoplasms

Carcinoma, Renal Cell

Glioblastoma

Sarcoma

Mesothelioma

Mesothelioma, Malignant

Wilms Tumor

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Soft Tissue Sarcoma

Malignant Mesothelioma

Wilms' Tumor

4 biweekly intradermal DC injections of 10\*10E6 DCs (500 µL) at 5 sites (100 µL/site) in the ventromedial regions of the upper arm approximately 5-10 cm of the regional lymph nodes

The aim of this study is to evaluate the immunogenicity and clinical efficacy of intradermal vaccination with autologous RNA-modified dendritic cells (DCs) - engineered to express the WT1 protein - in patients with limited spread metastatic solid tumors, i.e. breast cancers, glioblastoma grade IV, sarcomas, malignant mesothelioma and colorectal tumors. Based on the results of our previously performed phase I study with autologous WT1 mRNA-transfected DC, the investigators hypothesize that the vaccination with DC will be well-tolerated and will result in an increase in WT1-specific CD8+ T cell responses.

Dendritic Cell Vaccination for Patients With Solid Tumors

Therapeutic Efficacy of Wilms' Tumor Gene (WT1) mRNA-electroporated Autologous Dendritic Cell Vaccination in Patients With Solid Tumors: a Phase I/Feasibility Study

Immunogenicity of intradermal DC vaccination (cellular + humoral immunity against WT1 antigen) as measured by:

1. In vivo cytokine response (serum concentration of cytokines)
2. In vivo anti-WT1 antibody responses
3. In vitro T cell reactivity towards MHC class I and II-restricted WT1 epitopes by multiplex-cytokine assay using peripheral blood and DTH-infiltrating T cells
4. Delayed type hypersensitivity (DTH) responses
5. Quantitative and qualitative FACS analysis of WT1-specific-positive CD8+ T cells using HLA-A2 WT1 multimers

University Hospital, Antwerp

Breast Diseases

Px will receive standard neoadjuvant chemotherapy plus active vaccination. we will compare results with an historic cohort of patients treated with the same chemotherapy without the vaccines

Autologous dendritic cell vaccination. Dendritic cells are pulsed with their own tumor antigens

Autologous dendritic cell vaccination

Marta Santisteban, MD, PhD.

Molecular expression in breast cancer (BC) defines special fenotypes with different prognostic and predictive features.Since the addition of trastuzumab and lapatinib to chemotherapy, HER2 overexpressing tumors have become the best responders to systemic therapies, reaching pathologic complete response rates (pCR) around 50%. But HER2 negative tumors (luminal A and triple negative) are characterized by low chemosensitivity (luminal A) or early distant relapse after diagnosis (triple negative BC) . In this open, prospective, non-randomized and multicentric phase II study the investigators include stage II and III HER2 negative BC patients that are going to receive neoadjuvant sequential chemotherapy Epirubicin+Ciclofosfamide x 4 and then Docetaxel x 4)with an individualized vaccination with autologous dendritic cells pulsed with their own tumor. The hypothesis is that the reinforcement of the immune system with the autologous dendritic cell vaccination against HER2 negative BC could increase pathologic complete responses (pCR) and disease free survival(DFS), when added to chemo, surgery and radiation therapy and in a maintenance schedule.

Chemotherapy schedule:

* dose dense epirubucin 100 mgr/m2 plus ciclofosfamide 600 mgr/m2 every two weeks for four cycles with with GM-CSF support on day +1 (pegylated filgastrim) or on days +5 to +9 (filgastrim) subcutaneously
* docetaxel 80-100 mgr/m2 every three weeks for four cycles. Addition of GM-CSF if docetaxel doses are \> 85 mgr/m2

Trial With Autologous Dendritic Cell Vaccination in Patients With Stage II-III HER2 Negative Breast Cancer

Phase II Trial With Autologous Dendritic Cell Vaccination in Patients With Stage II-III HER2 Negative Breast Cancer

By 2017 scientific data should be communicated

We will compare our cohort of patients vaccinated and treated with chemotherapy, surgery and radiation therapy with an historic cohort in our center treated with the same schedule of chemotherapy , surgery and radiation therapy without the vaccine

Specific immune response will be evaluated as delayed hipesrsensitivity (DTH), humoral response by cuantification antibodies against tumoral cells (ELISA)and cellullar response (proliferation assay and citokines production)

Spanish Clinical Research Network - SCReN

National Institutes of Health (NIH)

Clinica Universidad de Navarra, Universidad de Navarra

MD, PhD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Toll-like Receptor (TLR) Ligand Matured Dendritic Cell Vaccination in Melanoma Patients	NCT00940004	Melanoma	autologous dend...	18 Years - 70 Years	Radboud University Medical Center
Dendritic Cell Vaccination for Patients With Solid Tumors	NCT01291420	Glioblastoma Renal Cell Carc... Sarcomas Breast Cancers Malignant Mesot... Colorectal Tumo...	autologous dend...	18 Years -	University Hospital, Antwerp
Trial With Autologous Dendritic Cell Vaccination in Patients With Stage II-III HER2 Negative Breast Cancer	NCT01431196	Stage II Breast... Stage III Breas...	Autologous dend...	18 Years - 75 Years	Clinica Universidad de Navarra, Universidad de Navarra

Spots Global Cancer Trial Database for autologous dendritic cell vaccination