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 BTU
The BTU is producing TIL products for an European multi-center
phase III trial with TIL therapy which started in 2014.
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 BTU 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
Circular plasmid DNA, produced and isolated from Escherichia
Coli, has several appealing clinical applications. The BTU is able
to produce GMP grade plasmid DNA that can be used in clinical
Several DNA products that have been produced by the BTU have been
used for a DNA vaccination trials 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.
In collaboration with NKI-AVL scientist, medical doctors
and other collaborators, we are constantly exploring new treatment
options. Together with the NKI-AVL and NEON Therapeutics
(Cambridge, MA) we are currently developing a neo-antigen directed
T cell product. This will hopefully result in a new generation of
personalized T cell therapy.
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. Case Report of a
Fatal Serious Adverse Event Upon Administration of T Cells
Transduced With a MART-1-specific T-cell Receptor. Mol Ther. 2015
Gomez-Eerland R, Nuijen B, Heemskerk B, van Rooij N, van den
Berg JH, Beijnen JH, Uckert W, Kvistborg P, Schumacher TN, Haanen
JB, Jorritsma A. Manufacture of gene-modified human T-cells with a
memory stem/central memory phenotype. Hum Gene Ther Methods. 2014
van der Heijden I, Gomez-Eerland R, van den Berg JH, Oosterhuis
K, Schumacher TN, Haanen JB, Beijnen JH, Nuijen B. Transposon leads
to contamination of clinical pDNA vaccine. Vaccine. 2013 Jul
van der Heijden I, Beijnen JH, Nuijen B. Long term stability of
lyophilized plasmid DNA pDERMATT. Int J Pharm. 2013 Sep
Oosterhuis K, Aleyd E, Vrijland K, Schumacher TN, Haanen JB.
Rational design of DNA vaccines for the induction of human
papillomavirus type 16 E6- and E7-specific cytotoxic T-cell
responses. Hum Gene Ther. 2012 Dec;23(12):1301-12
Henken FE, Oosterhuis K, Öhlschläger P, Bosch L, Hooijberg E,
Haanen JB, Steenbergen RD. Preclinical safety evaluation of DNA
vaccines encoding modified HPV16 E6 and E7. Vaccine. 2012 Jun
van den Berg JH, Oosterhuis K, Hennink WE, Storm G,
van der Aa LJ, Engbersen JF, Haanen JB, Beijnen JH,
Schumacher TN, Nuijen B. Shielding the cationic charge of
nanoparticle-formulated dermal DNA vaccines is essential for
antigen expression and immunogenicity.
J Control Release. 2010 Jan 25;141(2):234-40.
van den Berg JH, Nujien B, Beijnen JH, Vincent A, van
Tinteren H, Kluge J, Woerdeman LA, Hennink WE, Storm G, Schumacher
TN, Haanen JB. Optimization of intradermal vaccination by
DNA tattooing in human skin. Hum Gene Ther. 2009
Quaak SG, van den Berg JH, Toebes M, Schumacher TN, Haanen JB,
Beijnen JH, Nuijen B. GMP production of pDERMATT for vaccination
against melanoma in a phase I clinical trial. Eur J Pharm Biopharm.