Download Second meeting of the Spanish Immunotherapy Group

Cancer Immunol Immunother
DOI 10.1007/s00262-015-1732-2
MEETING REPORT
Second meeting of the Spanish Immunotherapy Group
GEIT (Grupo Español de Inmunoterapia), January 16, 2015,
in Zaragoza, Spain
Alberto Anel1 · Luis Martínez‑Lostao1 · Julián Pardo2 Received: 27 February 2015 / Accepted: 4 June 2015
© Springer-Verlag Berlin Heidelberg 2015
Keywords Immunotherapy · Cancer · Rheumatoid
diseases · Vaccines
Abbreviations
Apo2L/TRAILApo2 ligand/TNF-α-related apoptosisinducing ligand
CIBA
Centro de Investigación Biomédica de
Aragón (Centre for Biomedical Research
of Aragón)
CIMACentro de Investigación Médica Aplicada
(Centre for Applied Medical Research)
CNICCentro Nacional de Investigaciones Cardiovasculares (Spanish National Centre
for Cardiovascular Research)
CNIO
Centro Nacional de Investigaciones
Oncológicas (Spanish National Centre
for Cancer Research)
DNGR-1Dendritic cell NK lectin group receptor 1
ESAT-6Early secreted antigenic target of 6 kDa
FDAFood and Drug Administration
GEITGrupo Español de Inmunoterapia (Spanish Immunotherapy Group)
HBVHepatitis B virus
IISInstituto de Investigación Sanitaria (Institute for Health Research)
MTBVAC
Mycobacterium tuberculosis vaccine
* Alberto Anel
[email protected]
1
Departamento de Bioquímica y Biología Molecular y Celular,
Facultad de Ciencias, Universidad de Zaragoza, Campus Pza,
San Francisco, C/Pedro Cerbuna s/n, 50009 Saragossa, Spain
2
Institute of Health Research (IIS) of Aragon, Saragossa,
Spain
PD-1Programmed death 1
poly I:CPolyinosinic: polycytidylic acid
SEI
Sociedad Española de Inmunología
(Spanish Society for Immunology)
The Spanish Immunotherapy Group (GEIT) is a thematic
group created in 2013 inside the Spanish Society for Immunology (SEI), which intends to promote research and dissemination of immunotherapy and to foster collaboration
between basic and clinical researchers in this field, currently with 70 members. The second scientific meeting of
the GEIT was organized by Alberto Anel and Julián Pardo
under the auspices of the Institute of Health Research (IIS)
of Aragon and its scientific director Angel Lanas, and moderated by Julián Pardo [Centre for Biomedical Research of
Aragon (CIBA), Zaragoza] and Ignacio Melero [Centre for
Applied Medical Research (CIMA), Pamplona], and took
place on Friday January 16, 2015. The interest in the scientific program of the session was patent, involving 100
researchers, basic and clinical. This meeting was in part
intended to foster ties with other scientific societies related
to immunotherapy, since the GEIT is intended as a crosssociety group, not restricted to members of the Spanish
Society of Immunology (SEI). For this reason, and for their
scientific reputation, Carlos Martín, member of the Spanish Society for Microbiology, Ana Ortiz, belonging to the
Spanish Society for Rheumatology, and Marisol Soengas,
member of the Spanish Association of Bio-Enterprises,
were invited as speakers.
In the morning session, Carlos Martín (University of
Zaragoza) spoke about the latest developments on MTBVAC (Mycobacterium tuberculosis vaccine), the vaccine
against tuberculosis that his group has been developing
for over 15 years. MTBVAC is an attenuated mutant of M.
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tuberculosis, obtained by molecular biology techniques,
deleting the phoP gene, which regulates crucial virulence
factors of the pathogen, such as the secretion of the early
secreted antigenic target of 6 kDa (ESAT-6). After a century of use of the present vaccine BCG of bovine origin
(Mycobacterium bovis) with a poor protection against respiratory tuberculosis, MTBVAC is the first live attenuated
vaccine of human origin in clinical trials in humans with a
safe and strong immunological profile. Next, David San‑
cho [Spanish National Centre for Cardiovascular Research
(CNIC), Madrid] focused on how myeloid cells initiate
and modulate immunity and inflammation by sensing damaged-self and non-self components. Infection is frequently
associated with tissue damage, but knowledge about how
concomitant sensing of cell death by myeloid cells affects
the immune and inflammatory response to infection is limited. Dendritic cell NK lectin group receptor 1 (DNGR-1,
also known as CLEC9A) is a receptor selectively expressed
on dendritic cells. DNGR-1 detects ligands exposed upon
necrosis and potentially modulates the immune response to
infection. Dr. Sancho, using knockout mouse models and in
vivo immunizations, showed that DNGR-1 is essential for
regulation of cross-presentation against viral antigens, even
in the presence of a strong viral adjuvant during Vaccinia
virus infection. This topic is important for vaccination, as
most research is currently focused on adjuvants to get better vaccines and these results show that DNGR-1 sensing
tissue damage that is concomitant with infection potentiates viral antigen cross-presentation, offering a novel point
of intervention for vaccination. Further, he showed that
DNGR-1-mediated cross-presentation is crucial for secondary responses.
Rafael Sirera (Polytechnic University of Valencia)
showed data on the role of so-called regulatory T cells in
tumor development. The general idea in the scientific literature is that the infiltration of these cells into the tumor
tissue, or their predominance to the detriment of effector
T cells, is associated with a worse prognosis of the disease. However, Dr. Sirera’s studies using high-throughput
genetic analysis in the stromal compartment and in the
tumor itself combined with histological analysis, do not
confirm this conclusion in all cases, indicating that perhaps other histological and/or genetic parameters should be
analyzed to refine its prognostic value. Of particular interest was the talk of Lorena Yapur (Bristol-Myers Squibb,
Madrid) who updated the available clinical data on the
effectiveness of antibodies that prevent deactivation of the
immune system in the treatment of various cancers, the socalled checkpoint inhibitors. She stressed the importance
of ipilimumab, an anti-CTLA4 antibody, which is being
used successfully in the clinic against advanced melanoma
and is in clinical trials for other tumors, such as castrationresistant prostate cancer, metastatic renal carcinoma, and
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Cancer Immunol Immunother
other advanced solid tumors such as liver and lung cancer.
Moreover, the US Food and Drug Administration (FDA)
has recently approved the anti-programmed death 1 (PD1)
antibody nivolumab, as a result of clinical trials in melanoma. Finally, Dr. Yapur showed data from a clinical trial
that combines both antibodies in advanced melanoma, with
evidence of clinical activity in 65 % of patients. At the
maximum doses that were associated with an acceptable
level of adverse events, 53 % of patients had an objective
response, all with tumor reduction of 80 % or more.
In the afternoon session, Ana Ortiz (Hospital de la
Princesa, Madrid) gave an overview of the effect of immunotherapy in the field of rheumatology and its promising future. She stressed that a new era should be considered in the treatment of rheumatic diseases as a result of
the introduction of immunotherapy, which were introduced
some 15 years ago for rheumatoid arthritis. Before immunotherapy treatments were available, rheumatoid arthritis
was treated with non-specific immune suppressors, with
no other possibilities if patients became refractory to them.
Nowadays, a whole battery of immunotherapies are used,
specifically blockers of TNF-α such as infliximab, etanercept, adalimumab, certolizumab, and golimumab; blockers of IL-6, such as tocilizumab; blockers of IL-1, such as
anakinra; costimulation modulating drugs such as abatacept; or anti-CD20 antibodies, such as rituximab. This provides an important opportunity for physicians to use new
treatments if patients become refractory to the initial ones.
Returning to the treatment of melanoma, María S. Soen‑
gas (Spanish National Centre for Cancer Research (CNIO),
Madrid) explained the dramatic effects of a new treatment
based on stimulation of the immune system with nanocomplexes carrying polyinosinic: polycytidylic acid (poly I:C)
in melanoma. Although poly I:C is an agent that has been
used traditionally as an activator of the immune system
(e.g., NK cells), the mechanism of action of these nanocomplexes is different. Poly I:C nanocomplexes induce an
exacerbation of autophagy in tumor cells, finally resulting
in apoptosis and tumor regression. These results led to the
creation of a spin-off company, which intends to initiate
clinical trials shortly. Also, Marianna Di Scala (CIMA,
Pamplona) showed data on new immune-stimulating treatments for hepatitis B, based on gene transfer to the liver
of the cytokines interleukin-15 and interferon-α. Data presented showed that the combined administration of these
cytokines is able to break tolerance against viral antigens
in a transgenic mouse model of chronic hepatitis B and
to eliminate viral infection. Additionally, in collaboration with the group of Dr. Mala Maini from the Imperial
College London, they have found that the combination of
both cytokines can restore functional specific lymphocytes
against HBV. These data indicate that the combination
therapy with interleukin-15 and interferon-α may represent
Cancer Immunol Immunother
an alternative in patients who do not respond to current
therapies. Finally, Luis Martínez-Lostao (University of
Zaragoza) reviewed new alternative cancer treatments
based on one of the mechanisms used by the immune
system to eliminate infected or tumor cells, the so-called
death ligands. Specifically, this group has patented administering Apo2 ligand/TNF-α-related apoptosis-inducing
ligand (Apo2L/TRAIL) anchored on the surface of artificial
liposomes, which mimic the lipid composition of natural
exosomes in which this molecule is secreted by activated
human T lymphocytes. The anchoring of this ligand to a
lipid surface increases its pro-apoptotic activity, which is
largely lost if administered in soluble form. Clinical trials
against tumors made so far with Apo2L/TRAIL have used
the soluble form, with not very convincing results. In this
regard, it is interesting to note that these liposomes are
able to kill tumor cells that are even resistant to classical
chemotherapy.
Future directions in the field, also suggested in the discussions of the meeting, will be, especially in the field of
cancer immunotherapy, immune cell-activating antibodies
such as anti-CD137, antibodies targeting multiple myeloma
for NK cell-mediated cytotoxicity such as anti-CS1, or
antibodies blocking inhibitory receptors in NK cells, such
as anti-KIR, all of them in clinical trials at the moment. On
the other hand, although this subject was not treated in the
meeting, the use of T cells with chimeric antigen receptors
against a variety of tumors is also a big next wave in cancer
immunotherapy. All these advances have contributed to the
selection of tumor immunotherapy as the most important
scientific advance in 2013 by Science journal.
It is clear that good times for immunotherapy are running, and in a few years, this will be a real alternative in the
treatment of many diseases, in addition to those that were
already treated in this way. The GEIT and their members
expect to be there to see it and to participate actively in this
small revolution.
Acknowledgments Bristol-Myers Squibb and Miltenyi Biotec
funded this scientific event.
Conflict of interest The authors declare no conflict of interest.
Alberto Anel and Julián Pardo were conference organizers.
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