Products

TIL

Tumor Infiltrating Lymphocytes (TIL), isolated and expanded from fresh tumor material can be a potent immunotherapeutic treatment option for metastatic melanoma patients. This treatment, developed at the National Cancer Institute, Bethesda, MD, is now used in several centers in the US, Europe and Israel. Our team has implemented the so-called “young TIL” process in the AmBTU facility.

The AmBTU is producing TIL products for an European multi-center phase III trial with TIL therapy which started in 2014.

Gene modified T cells

Infusion of patient T cells that have been genetically modified with tumor-reactive T cell receptors (TCR), so called TCR gene therapy, is an appealing immunotherapeutic strategy. TCR gene therapy can be used when tumor material is not available for the isolation of tumor-reactive T cells or in case tumor-reactive T cells cannot be expanded from such material.

In addition, TCR gene therapy allows the use of a set of particularly effective TCR genes in large patient groups. Furthermore, TCR gene therapy has the potential to treat patients with T cell populations that have an increased capacity for long-term engraftment, relative to the highly differentiated cell populations that are generally found within TIL.

The AmBTU/NKI-AVL has designed and validated a process to retrovirally transduce autologous T cells with a tumor specific TCR. This process is now used to produce cell products for a phase I/II trial in metastatic melanoma patients, conducted at the NKI-AVL in Amsterdam.

In addition, the AmBTU is pleased to be involved in the EU funded FP7 consortium ATTACK. In this consortium, the AmBTU will produce TCR modified T cells for two clinical trials. In the first trial, the tumor reactivity of these cells will be determined in eosophago-gastric cancer. The second trial will be conducted in metastatic melanoma patients. For more information: see section Collaborations

Plasmid DNA

Circular plasmid DNA, produced and isolated from Escherichia Coli, has several appealing clinical applications. The AmBTU is able to produce GMP grade plasmid DNA that can be used in clinical trials.

The first plasmid DNA that was produced by the AmBTU has been used for a DNA vaccination trial at the NKI-AVL.

The AmBTU is pleased to be involved in the EU funded FP7 consortium RAID. In this consortium, the AmBTU is responsible for the production of clinical grade plasmid DNA for two clinical trials conducted at the department of gynaecology at the NKI-AVL.

Besides DNA vaccination, plasmid DNA can also be used to genetically modify target cells as an alternative for expensive and laborious viral vectors.

About us

  • The AmBTU is a spin-off entity of the divisions of Immunology and Pharmacology at the Netherlands Cancer Insititute – Antoni van Leeuwenhoek (NKI-AVL).
  • Three dedicated, fully equipped and state-of-art class A/B cleanrooms are available for the AmBTU to produce biotherapeutics under full Good Manufacturing Practice (GMP).
  • We are particularly experienced in the production of T cell products and plasmid DNA, but we are also interested to further expand the current product portfolio.
  • The AmBTU is producing products for clinical trials performed by academic partners and is especially experienced in the translation of lab derived protocols to a clinical production process.

Joost van den Berg

Director

Maaike van Zon

Technician

Jos Beijnen

Founder and Head of the Board of Directors

Professsor Analytical Drug Toxicology, Hospital Pharmacist, Qualified Person

 

Bastiaan Nuijen

Founder and member of the Board of Directors

Hospital Pharmacist, responsible for GMP 

John Haanen

Founder and member of the Board of Directors

Professor in Translational Immunotherapy, Medical Oncologist

Ton Schumacher

Founder

Professor in Immune Technology

Noor Bakker

Technician

Collaborations

FP7 RAIDs

As a partner in the FP7 RAIDs consortium, the AmBTU is currently producing DNA vaccines for clinical studies in patients with HPV derived malignancies.

FP7 ATTACK

The AmBTU will produce NY-ESO-1 T cell receptor modified T cells for the FP7 ATTACK consortium.

NKI-AVL

The AmBTU is currently producing DNA vaccines, TILs and T cell receptor modified T cells for clinical studies performed at the NKI-AVL.

FP7 TargetAMD

For the FP7 EU consortium TargetAMD, AmBTU is developing and producing clinical grade plasmid vectors for ex vivo transfection of retina cells.

These plasmids will be used in a phase I trial in patients with Age Related Macular Degeneration (AMD).

Publications

Long term stability of lyophilized plasmid DNA pDERMATT.

van der Heijden I, Beijnen JH, Nuijen B.

Transposon leads to contamination of clinical pDNA vaccine.

van der Heijden I, Gomez-Eerland R, van den Berg JH, Oosterhuis K, Schumacher TN, Haanen JB, Beijnen JH, Nuijen B.

Rational design of DNA vaccines for the induction of human papillomavirus type 16 E6- and E7-specific cytotoxic T-cell responses.

Oosterhuis K, Aleyd E, Vrijland K, Schumacher TN, Haanen JB.

Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7.

Henken FE, Oosterhuis K, Öhlschläger P, Bosch L, Hooijberg E, Haanen JB, Steenbergen RD.

Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7.

Oosterhuis K, Ohlschläger P, van den Berg JH, Toebes M, Gomez R, Schumacher TN, Haanen JB.

Naked plasmid DNA formulation: effect of different disaccharides on stability after lyophilisation.

Quaak SG, Haanen JB, Beijnen JH, Nuijen B.

Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity.

van den Berg JH, Oosterhuis K, Hennink WE, Storm G, van der Aa LJ, Engbersen JF, Haanen JB, Beijnen JH, Schumacher TN, Nuijen B.

Lipopolysaccharide contamination in intradermal DNA vaccination: toxic impurity or adjuvant?

van den Berg JH, Quaak SG, Beijnen JH, Hennink WE, Storm G, Schumacher TN, Haanen JB, Nuijen B.

DNA tattoo vaccination: effect on plasmid purity and transfection efficiency of different topoisoforms.

Quaak SG, van den Berg JH, Oosterhuis K, Beijnen JH, Haanen JB, Nuijen B.

Optimization of intradermal vaccination by DNA tattooing in human skin.

van den Berg JH, Nuijen B, Beijnen JH, Vincent A, van Tinteren H, Kluge J, Woerdeman LA, Hennink WE, Storm G, Schumacher TN, Haanen JB.

Development and validation of an anion-exchange LC-UV method for the quantification and purity determination of the DNA plasmid pDERMATT.

Quaak SG, Nuijen B, Haanen JB, Beijnen JH.

GMP production of pDERMATT for vaccination against melanoma in a phase I clinical trial.

Quaak SG, van den Berg JH, Toebes M, Schumacher TN, Haanen JB, Beijnen JH, Nuijen B.

Microbead-assisted retroviral transduction for clinical application.

Heemskerk B, Jorritsma A, Gomez-Eerland R, Toebes M, Haanen JB, Schumacher TN.

Selecting highly affine and well-expressed TCRs for gene therapy of melanoma.

Jorritsma A, Gomez-Eerland R, Dokter M, van de Kasteele W, Zoet YM, Doxiadis II, Rufer N, Romero P, Morgan RA, Schumacher TN, Haanen JB.

Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype.

Gomez-Eerland R1, Nuijen B, Heemskerk B, van Rooij N, van den Berg JH, Beijnen JH, Uckert W, Kvistborg P, Schumacher TN, Haanen JB, Jorritsma A.

Case report of a fatal Serious Adverse Event upon administration of T cells transduced with a MART-1 specific T cell receptor.

van den Berg JH, Gomez-Eerland R, van de Wiel B, Hulshoff L, van den Broek D, Bins A, Tan HL, Harper JV, Hassan NJ, Jakobsen BK, Jorritsma A, Blank CU, Schumacher TN, Haanen JB.

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