Toward next-generation cancer immunotherapy: 10th Annual Meeting ...

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Jan 9, 2013 - Meeting of the Association for Cancer Immunotherapy (CIMT),. Mainz, Germany ... advances and trends in the field of cancer immunotherapy.
Cancer Immunol Immunother (2013) 62:975–981 DOI 10.1007/s00262-012-1386-2

MEETING REPORT

Toward next-generation cancer immunotherapy: 10th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Mainz, Germany, May 23–25, 2012 Bjo¨rn-Philipp Kloke • Sarah Kutscher • Richard Rae • Pia Kvistborg • Cedrik M. Britten Sine Reker Hadrup



Received: 18 September 2012 / Accepted: 11 December 2012 / Published online: 9 January 2013 Ó Springer-Verlag Berlin Heidelberg 2013

Introduction

Personalized medicine

With 620 international participants, more than 70 speakers and 216 abstracts, the 2012 Annual Meeting of the Association for Cancer Immunotherapy (CIMT) celebrated its 10th anniversary as the premier European meeting dedicated to research and development of cancer immunotherapy. The latest advances of the field were discussed in sessions on cellular therapies, immunomonitoring, new targets and leads, therapeutic vaccination, tumor biology and immune interaction. Here, we summarize the highlights of the meeting which were representative of the newest advances and trends in the field of cancer immunotherapy.

The 10th anniversary meeting especially highlighted the path to personalized cancer therapy. Translating promising research concepts into the clinic still faces a myriad of challenges. The complex application of novel technologies, biomarkers and immune monitoring, the demands of GMP manufacturing as well as regulatory questions continue to test researchers and developers alike. The CIMT 2012 meeting addressed these challenges in multiple sessions, providing key examples for the whole range of passively and actively personalized approaches to cancer therapy.

Personalized medicine—individualized vaccines

This meeting report is a summary of presentations from the Tenth Annual Meeting of the Association for Cancer Immunotherapy, CIMT 2012, published together with a series of Focussed Research Reviews based on lectures given at the conference. B.-P. Kloke (&)  C. M. Britten Ribological GmbH, Ho¨lderlinstraße 8, 55131 Mainz, Germany e-mail: [email protected] S. Kutscher Immatics Biotechnologies GmbH, Tu¨bingen, Germany R. Rae  C. M. Britten TRON–Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Mainz, Germany P. Kvistborg The Netherlands Cancer Institute, Amsterdam, The Netherlands S. R. Hadrup Center for Cancer Immune Therapy (CIMT), University Hospital Herlev, Herlev, Denmark

The opening lecture given by Pramod Srivastava (Farmington, USA) introduced the topic of personalized cancer vaccines. Providing a historic overview, Pramod Srivastava reminded the audience that George Klein had conducted experiments with methylchloranthrene-induced sarcomas more than 50 years ago. Klein had demonstrated that tumor protection in a primary tumor-bearing host was conferred by T cells recognizing unique tumor antigens that do not cross-react with other sarcomas. 20 years ago, Pramod Srivastava, himself a pioneer in cancer immunotherapy, had assumed that the described uniqueness of immunological tumor recognition arises from random tumor mutations. Although the hypothesis of immunogenic private tumor mutations has now been known for decades, only a few tumor antigen-specific mutations have been identified. According to Pramod Srivastava, Heat Shock Proteins (HSP) derived from autologous tumors constitute a personalized vaccine approach that (1) has the potential to immunize a patient with unique neo-epitopes derived

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from tumor mutations and (2) was clinically tested in multiple patients in different tumor entities. The vaccine concept was approved for the therapy of malignant melanoma in Russia and is currently being further developed in patients with glioblastoma in the United States. Despite promising results in patients when using HSP vaccines, it remains scientifically unsatisfying not to know what drives the immune responses of patients who respond to the treatment. Recent progress in technology enables whole genome sequencing at affordable costs, paving the way for studies on the role of tumor mutations in the process of immune editing. First proof-of-concept studies in mice confirmed the protective potential of private tumor mutations. As elegantly shown in ground-breaking mouse studies by Robert Schreiber (St. Louis, USA), the immune system does not only protect the host against tumor formation, but also shape tumor immunogenicity by immunoediting. Our current understanding of the function of tumor antigens was mainly derived from already edited tumors. Therefore, Robert Schreiber has recently focused specifically on demonstrating that T cell–dependent immunoselection is a mechanism which underlies the outgrowth of tumors that lack strong rejection antigens. He showed that the mutation of only one epitope may be responsible for tumor control and that immunoediting can produce tumor cells which lack this immunodominant epitope. The next question is: are tumors with strong driver mutations that have lost immunogenic antigens still immunogenic and therefore a valid target for cancer immunotherapy? If so, these antigens could serve as a basis for personalized tumor vaccinations. The proof-of-concept experiments conducted by Pramod Srivastava and Robert Schreiber are complementary to a landmark study published by Ugur Sahin (Mainz, Germany), encouraging the field to move on with a clinical translation in the near future. Ugur Sahin and colleagues showed protection of C57BL/6 mice from B16 melanoma tumor challenge following vaccination with a mutated peptide derived from mutanome sequencing. The biggest challenge for researchers and developers will be to define how to select the most immunogenic mutation candidates. Large systematic studies to enable rational mutation selection are currently underway. John Castle (Mainz, Germany) provided insight into these challenges and presented the development of a bioinformatics infrastructure. With this infrastructure, information can be handled on a per patient basis, combining next-generation sequencing, exome re-sequencing and immunogenicity analyses to enable deciphering of patient tumor-specific mutanomes. As proposed by Ugur Sahin, a pharmacologically optimized RNA vaccine platform might allow for a rapid and affordable generation of individualized poly-neo-epitopic

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vaccines that target multiple private tumor mutations. The combination of the analytical workflow for mutation selection with the rapid GMP manufacturing of multi-epitope vaccines provides a basis for the generation of personalized vaccine approaches. The concept of actively personalized vaccination (APVAC) using multiple peptides per patient is currently being investigated by Stefan Stevanovic´’s group (Tu¨bingen, Germany). They are exploring adjuvant tumor therapy for primary liver cancers, with the aim to overcome residual disease. So far, tumors from seven patients have been investigated in this manner. The group proposes to apply the combination of genetic mutation analysis by nextgeneration sequencing of individual tumors with a targeted search for the corresponding mutated peptides by mass spectrometry (MS). While next-generation sequencing allows the number of potential tumor-specific neo-epitopes to be narrowed down, making a targeted search by MS feasible, MS analysis has the potential to confirm that a given mutation-derived neo-epitope is indeed presented on tumor cells. Further experiments are needed to prove this appealing concept. Presenting one of the few examples of APVACs in the clinic, Kyogo Itoh (Kurume, Japan) gave an overview of his group’s development program of personalized peptide vaccination in castration-resistant prostate carcinoma and glioblastoma multiforme. He summarized several phase I/II clinical trials in which patients were vaccinated with up to four tumor-associated peptides (HLA class I epitopes) following a selection process based on pre-existing cellular or humoral immune responses. Generally, a correlation of immune responses and clinical benefit could be observed in the investigations. After a successful escalation of dosage and vaccination schedules, as well as the demonstration of safety and a first proof-of-concept, the groundwork is laid for personalized peptide vaccination assessment in a phase III trial. Next to Kyogo Itoh, Samir Khleif (Bethesda, USA) is one of the pioneers in the development of personalized vaccines that target individual tumor mutations. He has already published data from phase I trials, targeting individual ras, p53 and Von Hippel–Lindau gene mutations. Samir Khleif showed promising data from a new phase II trial, with three shelved peptide antigens targeting different ras mutations that can cover approximately 90 % of patients with colon and pancreatic cancer.

Personalized medicine—biomarker guidance The personalized approach is also being used to identify biomarkers predictive for disease progression, response to therapy or development of adverse effects. Recent investigations have led to considerable progress in

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biomarker assessment. Thus, biomarkers are increasingly used to guide oncologists in the selection of therapies according to a patient’s individual cancer and prognosis. Likewise, biomarkers play a prominent role in tailoring cancer immunotherapy and in predicting its therapeutic success. One of the most prominent findings in this regard is the work by Jerome Galon (Paris, France). He showed how routinely used tumor staging (AJCC/UICC-TNM classification) can be improved by incorporating the immune contexture of tumors as a prognostic factor. Based on his pioneering work on colorectal cancer, he reported on the ongoing development of an international task force dedicated to the evaluation, harmonization and validation of Immune Scoring as a new approach to cancer classification. The generated data suggests that the immune system does play a role for prognosis of a wide range of cancer types. It gives rise to the hope that a systematic application of the immunoscore may become a generally applied biomarker with prognostic or even predictive value. Another strategy for biomarkers in cancer is based on a molecular analysis of circulating tumor cells (CTC). Klaus Pantel (Hamburg, Germany) described how the identification of CTC has technically improved over the last couple of years and is now increasingly acknowledged for determining the risk of metastasis and relapse after a period of dormancy. Thus, CTC assessment is currently used in over 400 trials. He furthermore emphasized the potential of CTC for identifying therapeutic targets in a patient-individualized manner. Heterogeneous marker expression and a potentially occurring epithelial–mesenchymal shift of CTC provide challenges in detecting CTC and point out the need for more complex assays. On the other hand, detailed functional and phenotypic characterization also provides opportunities to further sharpen the predictive value of CTC measurement as a biomarker, therapeutic monitoring tool and, most importantly, as a tool for identifying novel target structures for immunotherapy, particularly in an adjuvant setting. Thomas Gajewski (Chicago, USA) nicely showed that a T cell–inflamed tumor microenvironment may also serve as a predictive biomarker for response to immunotherapies. In his feature lecture, he presented data indicating that in many cases, tumor infiltrating T cells are not capable of rejecting the tumor due to local immune-suppressive mechanisms (PD-L1, IDO, Tregs) acting in the tumor microenvironment. He presented data to support the hypothesis that in fact the expression of IDO and PD-L1, and the accumulation of Tregs, may depend upon the infiltration of CD8? T cells in the tumor site. Clinical applications to target these immune-suppressing factors are currently investigated by him and others (see also section on immunomodulatory agents).

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Personalized medicine—state-of-the-art immunomonitoring The new strategies for personalized immunotherapy with biomarker guidance lead to increasing complexity in immunomonitoring. Scott Tanner (Toronto, Canada) presented CyTOF as a new technology to analyze the phenotype of cells using monoclonal antibodies labeled with stable isotopes, primarily of lanthanides. Flow cytometry is limited by the number of available detectors per instrument, the need for compensation of spectral overlap and the natural limit of the light spectrum; mass cytometry overcomes these limitations to a certain degree by replacing fluorophores with these metal tags and allows for parallel assessment of up to 42 different parameters (with potential to exceed 100). An automated software (SPADE) has been generated to enable comprehensive data handling. This new technology can, for example, be used to identify different populations and place similar populations and related phenotypes in proximity to each other. This forms a tree-like structure of related cell populations with lymphocytes branching out into NK cells, B cells, T cells etc. and further sub populations branching out from each new population. This technique allows for easy identification of the effect of external stimuli on different cell populations. Data handling and analysis has become an increasing challenge, as current flow cytometry has reached a level where over 10 parameters are routinely analyzed, and up to 20 parameters may be used with certain flow cytometers. The standard method of analysis is to manually examine data distributions using 2 dimensions at a time. Obviously, when more parameters are studied, the number of twodimensional plots required to identify every possible population becomes very high, making the analysis labor intensive. Richard Scheuermann (San Diego, USA) talked about the effort to develop automatic analysis algorithms for flow cytometry data. New algorithms have been published that can be used to identify all possible populations based on all parameters included in the experiment by simultaneously analyzing data in an N-dimensional space. One such approach uses the FLOCK (flow cytometry clustering without K) algorithm. Richard Scheuermann and co-workers showed that this software could automatically find 17 different B-cell populations, each with a unique phenotype, when using a 10-parameter B-cell panel. The FLOWCAP consortium has tested several automatic cytometry analysis algorithms in a comparison by using expert manual gating as a golden standard. They developed methods that performed well with simple datasets. Successful results could even be obtained with more complex datasets, suggesting that automated gating will be very accurate and reproducible in the future, as it removes

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the human variability and subjectivity in the analysis of flow cytometry data. The quality and reproducibility of the assays and protocols used are crucial for monitoring immune parameters related to clinical interventions. Sine Reker Hadrup (Herlev, Denmark) gave an update on the recent CIP MHC multimer panel, focusing on comparing PE, APC, QD605 and QD705 conjugated peptide-MHC (pMHC) multimers. Based on the staining index of the pMHC multimer population, PE was the brightest, APC and QD605 were comparable and QD705 was the dimmest fluorochrome. The chosen fluorochromes did generally not affect the ability to identify positive populations. In this proficiency panel, a set of fluorescence-labeled beads were included and proved useful in predicting how the setup of the flow cytometer and design of the antibody panel affected the readout of a multimer panel. This can be a very useful tool for optimizing the instrument and experimental design. The use of reference samples is an appealing solution to control the quality of various parameters over time. Nicole Bidmon (Mainz, Germany) described how this was addressed in a proficiency panel by using NY-ESO-1 and tyrosinase T-cell receptor RNA–transfected T cells. The quantification of these reference samples was successfully performed both by ELISPOT assay and pMHC multimer staining, enabling the use of reference samples in clinical trials as a quantitative positive control. This would allow the variable staining of patient samples to be referenced against known reference samples, minimizing variability over time. As a new initiative by the CIP working group, Steffen Walter (Tu¨bingen, Germany) introduced the upcoming Myeloid Derived Suppressor Cell (MDSC) panel. These cell populations have shown to be of great importance: data generated by Steffen Walter and his group, among others, have shown that the level of certain MDSC populations correlate with clinical outcome in cancer immunotherapy trials. It will be the first non-T-cell CIP panel, and several markers have been suggested for the identification of MDSCs.

Personalized medicine—regulatory challenges Personalized medicine and new technologies for the identification of biomarkers that are used to select patient populations offer a number of regulatory challenges. Ulrich Kalinke (Hanover, Germany) and Cedrik Britten (Mainz, Germany) provided an update on the activities of the CIMT regulatory research group (RRG). About 2 years ago, RRG embarked on a project to address the regulation of personalized medicines. Clear regulatory guidance for APVACs targeting multiple mutated antigens for individual

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patients does not exist. RRG proposed to guide regulatory principles for such approaches that may apply independently to a specific product development, and which were discussed at a Briefing Meeting with EMA’s Innovation Task force. The official minutes of this meeting are now available and can be downloaded from the CIMT homepage. Notably, RRG reached the conclusion that vaccines targeting multiple individual tumor mutations can indeed be developed under current European legislation. According to Samir Khleif regarding the further development of mutanome-based cancer vaccines, the regulatory focus in the United States will most likely be put on companion diagnostics and devices applied to identify, validate and select the mutations for patient-specific vaccines. The FDA has drafted a guidance document on this important issue (http://www.fda.gov/downloads/MedicalDevices/Device RegulationandGuidance/GuidanceDocuments/UCM262327. pdf). As a result of this new guidance, the FDA will review each companion-diagnostic device submission within the context of its corresponding therapeutic product. Consequently, therapeutic vaccines will not be given marketing approval, if the diagnostic assay has not been approved. Peter Bross (Rockville, USA) confirmed the importance of clinical validation of in vitro diagnostic devices (IVDDs), which should happen at phase III of the clinical development of a therapeutic drug. As the center for biological evaluation and research (CBER) and the center for devices and radiological health (CDRH) will be in charge and do not necessarily share databases, separate preInvestigational New Drug (IND) application meetings might be needed. In any case, early meetings with regulatory bodies should be encouraged. According to Bruno Flamion (Namur, Belgium), the situation in the EU is different, since EMA does not formally regulate IVDDs. Although EMA does not want to change the principle that national notified bodies will continue to regulate IVDDs in the EU, it may well be that EMA, upon approval of new therapeutic treatments that involve the use of IVDDs, will have a clear opinion on the quality and validation status of analytical assays. In summary, drug developers in the EU will probably see increasing standards that will become similar to requirements established in the United States. Despite the differences between regulatory frameworks in Europe and the United States, the world will probably see the first mutanome-based vaccines tested in patients in the coming years.

Boosting immunity—immunomodulatory agents To improve efficacy of personalized approaches for modulation of the immune system, several immunomodulatory compounds have been proposed to boost immunity.

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CTLA-4-targeted antibody therapy, being the first approved strategy in this category, has been studied in detail by James P. Allison (New York, USA). CTLA-4 blockade increases infiltration of tumors by CD4? and CD8? effector cells and enhances tumor-specific immune responses. In his presentation, James P. Allison described some of the possible future combinations for the antiCTLA-4 antibody Ipilimumab, including vaccines (e.g., GVAX, DNA, protein), the blockade of additional immune checkpoints (e.g., PD-1, PD-L1, B7-H3, B7-H4), conventional therapies, targeted therapies (PLX4032 targeting the common BRAF-mutations in malignant melanoma), androgen deprivation and stimulation of additional costimulatory pathways (e.g., ICOS). For the latter, James P. Allison showed that levels of ICOShigh CD4 T cells are increased in the tissue and blood of bladder cancer patients after anti-CTLA treatment. In melanoma patients, sustained ICOShigh T cells after anti-CTLA4 treatment are associated with survival benefit (20 vs. 8.1 months). Agonistic antibodies, such as anti-CD40 and anti-CD27, have recently reached the clinic and have introduced additional challenges in terms of level of activation. Martin Glennie (Southampton, UK) discussed the mechanism of action for a number of agonistic antibodies and the importance of Fc region interactions. Antibodies may additionally be used to target antigens to dendritic cells or induce the recruitment of these immune stimulatory cells to boost anti-tumor immunity against specific antigens.

Boosting immunity—chemotherapy as combination Chemotherapy or radiotherapy may affect the immunological balance at the tumor site which has important application both for the effect of these treatments and for combination therapy. Laurence Zitvogel (Villejuif, France), who pioneered the concept that chemotherapy or radiotherapy both can mediate anti-tumor effects at least partly through the immune system, showed the latest results on the mechanisms of immunogenic cell death that translate into adaptive immune responses via innate effectors. After having found that immunogenic cell death is characterized by the pre-apoptotic exposure of calreticulin on the cell surface, post-apoptotic release of HMGB1 and secretion of ATP, it could be shown that interaction of these molecules with their receptors on DC leads to IL-1b production followed by activation of IL-17-producing cd T cells and finally to CD8 T-cell infiltration. Thus, it became evident through a number of studies that IL-1b sets the stage as a master regulator of the inflammatory immune response and should be taken into account in the design of future immunotherapeutic strategies.

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As another means of boosting immune therapy, Mustafa Diken (Mainz, Germany) presented how the immunosuppressive drug rapamycin, which is the inhibitor of mTOR (mammalian target of rapamycin), can be employed to augment the potency of a RNA-based vaccine. Delayed rapamycin treatment after intranodal vaccination of naked antigen-encoding RNA changed the memory differentiation program and resulted in a higher frequency of CD8 memory T-cell precursors. Moreover, it altered the cellular tumor micro milieu, revealed by a higher capability of CD8 T cells to infiltrate the tumor as well as a lower frequency of intratumoral MDSCs, leading to an improved antitumoral potency after combination of vaccination with rapamycin.

Boosting immunity—combination with BRAF antagonists Several of the strategies for boosting immune therapy may be used in combination. The key features for successful combination therapies were outlined by Patrick Hwu (Houston, USA). Understanding the (1) in vivo effects of targeted therapies on immune cells (2) influence of specific oncogenic mutations on the tumor immune microenvironment and (3) effects of specific targeted inhibitors on the anti-tumor immune response, will be the key to increasing the overall survival of patients. Taking BRAF inhibition as an example for this concept, he showed that treatment with a BRAF inhibitor (GSK) does not affect CD4? and CD8? memory T-cell responses to recall antigens, but increased the number of antigen-specific T cells in treated patients. He further presented data which showed that several immune-related genes are induced by BRAFV600E. Its inhibition can specifically block IL-1a and IL-1b production in melanoma cells leading to a down-regulation of the immunosuppressive molecules PD-L1 and COX-2 in melanoma tumor–associated fibroblasts. The consequence is increased T-cell proliferation and decreased anergy in the tumor microenvironment. Following this line of argument, Patrick Hwu presented pre-clinical data on tumor-bearing mice which received anti-PD-1 and adoptive cell therapy (ACT) with antigenspecific T cells. Tumor progression in these mice was delayed due to an increased number of transferred T cells at the tumor site. He was able to transfer this knowledge to the combination therapy using ACT and the BRAF inhibitor PLX4720. Administration of PLX4720 was shown to increase infiltration of adoptively transferred T cells in tumors with BRAF mutation, but not in tumors with wt B-Raf, which is due to a BRAF-induced down-regulation of VEGF at the tumor site.

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Whether BRAF inhibitors synergise with immunotherapy is, however, still a matter of debate. Rienk Offringa (Heidelberg, Germany) presented contrasting data, which were collected with a genetic mouse model. In this model, the expression of BRAFV600E combined with Pten tumor suppressor gene silencing elicits development of skin melanoma. In these mice, therapeutic strategies were evaluated that combined either chemotherapy or small molecule BRAF inhibitors with immunostimulatory antibodies (agonistic anti-CD40, anti-CTLA-4). Whereas combination of chemotherapy with antibodies clearly resulted in synergy, the co-administration of BRAF inhibitors and antibodies did not yield increased efficacy compared to BRAF inhibitors alone. This is supported by findings from Christian Blank (Amsterdam, Netherlands) and his group, who used the same mouse model. Thus, it is not clear at present why some investigators discover immune-suppressive effects while others find immune stimulating effects for BRAF inhibitors. More studies to investigate the complex interaction of these compounds with the immune system are urgently needed.

Synthetic biology—antibody engineering at its best In addition to personalized vaccines and compounds to boost immunity, several lectures covered novel immune therapy approaches which are based on the engineering of antibody fragments, such as transfer of chimeric antigen receptor (CAR)-engineered T cells and bi-specific antibodies that enable engagement of T cells or confer dual specificity. Carl June (Philadelphia, USA) provided data on the first set of patients who were treated with CAR T cells a decade ago as a strategy against HIV. These CAR T cells, which were generated by c-retroviral vector engineering, persisted and showed no signs of insertional mutagenesis. Carl June showed that CARs persist and remain functional in HIV patients for at least a decade and at least 18 months in leukemic patients. More specifically, he provided evidence that CAR T cells directed against CD19 have a potent and durable clinical activity, with the drawback that the on-target cytokine release syndrome can be severe. The longevity of engineered T cells may lead to lifelong tumor cell control, but may also mean that any side effects of the T-cell transfer (e.g., B-cell depletion) may be difficult to control or eliminate. Most importantly, the unprecedented clinical effects observed in the treated CLL patients now justify larger clinical trials with anti-CD19 CARs in CLL patients and fuel the hope that CAR therapy may change clinical practice for hematological or even solid malignancies in the future.

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Another strategy to engage T cells to kill tumor cells is the use of bi-specific antibodies that direct T cells to tumors independent of their TCR-specificity. An example of such an approach, the BITE (bi-specific T-cell engager) antibodies, was presented by Tobias Raum (Munich, Germany). He presented a newly developed BITE antibody, with the antibody recognition part directed against the Epithelial cell adhesion molecule (EpCAM) that is overexpressed in the majority of solid tumors and the T-cell engagement part as the antigen recognition part of anti-CD3. Thus, these BITE antibodies crosslink CD3 T cells upon tumor cell engagement. This strategy is strictly target dependent, and a successful use of BITE antibodies is largely dependent on proper target selection. BITE antibodies have shown the ability to redirect lysis of cancer cells—including non-dividing cells. T cells engaged by these BITE antibodies have shown induced proliferation and ability to conduct serial lysis. Another BITE antibody, Blinatumomab, an anti-CD19–anti-CD3 antibody, has already been tested in the clinic. In a phase II trial for chemotherapy refractory minimal residual disease in B lineage acute lymphoblastic leukemia patients, this BITE construct has shown very promising responses rates, with more than 75 % of patients becoming minimal residual disease negative. The auspicious results observed in the patients treated with BITEs have led to the recent acquisition of Micromet by Amgen, that is, now proceeding with the clinical development of these highly promising reagents that are about to open new treatment options in the field of immune-oncology. The field is excited to see the next steps that may lead to the approval of a first BITE in the near future. The epidermal growth factor receptor family ErbB/HER has, for more than a decade, been used as a target for antibody therapy, with Herceptin/trastuzumab as the leading agent. Mark Sliwkowski (San Francisco, USA) presented some of the strategies that have recently completed pivotal phase III clinical testing. The combination of docetaxel, trastuzumab and another antibody against HER2 (pertuzumab/Perjeta) has shown over a 6-month period to improve the progression free survival in comparison with docetaxel and trastuzumab only. An antibody drug conjugate (ADC) of trastuzumab and emtansine was recently reported to be successful in a phase III trial. Finally, a new era of antibody therapy has started by the introduction of dual-specific (two-in-one) IgG molecules that enable simultaneous targeting and blockade of two signalling molecules. Such a dual-specific antibody that targets both the HER3 receptor and the EGFR has recently been developed and shown promise in pre-clinical and phase I testing. The agent is currently being tested in a phase II clinical trial.

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Keynote lecture Compared to the field of infectious diseases where vaccines have been commonly used for more than a century, cancer vaccines are still in their infancy. Yet much can be learned from the advances in understanding and treating infectious diseases. Promoting interaction between the two fields, CIMT invited Antonio Lanzavecchia (Bellinzona, Switzerland) to give a keynote lecture based on his outstanding experience in dissecting the human B- and T-cell immune response to pathogens. Starting with an introduction on high-throughput techniques for monoclonal antibody identification from human B cells and plasma cells, he introduced the concept of analytic vaccinology, showing examples from the search for broadly neutralizing antibodies overcoming the ‘‘golden rules of serotypes’’. Antonio Lanzavecchia then switched to T-cell immunology and introduced sophisticated methods to establish T-cell repertoire libraries starting from naı¨ve T cells for evaluation of immunogenicity or from memory T cells for antigen/target identification of pathogens and of tumors. He showed that ex vivo analysis and in vitro priming with whole pathogens results in the same functional patterns of T cells and varies considerably between different pathogens. He presented a study showing that Candida albicans and Staphylococcus aureus prime TH17 cells, which produce either IFN-c or IL-10. IL-1b and IL-2 could be identified as pro- and anti-inflammatory regulators of TH17

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cells both at the priming and in the effector phase. Thus, a further role of IL-1b as the pro-inflammatory master regulator was identified. The applicability of the pioneering studies conducted by Antonio Lanzavecchia’s group reaches far beyond the field of infectious diseases and inspires the work of tumor immunologists.

Concluding Remarks The vision of the CIMT community was, and is, to generate an interactive platform for the highly specialized yet interdisciplinary field of cancer immunotherapy. The 2012 meeting was a fitting celebration of CIMT’s 10th anniversary. Bringing together international opinion leaders from academic institutions, industry and regulatory agencies, and attracting participants from more than 30 nations, CIMT proved to be one of the most energetic and largest platforms in the field for knowledge exchange, scientific discourse and networking. Further investing in the future, CIMT has introduced travel awards and poster prices to recognize the outstanding contributions of young investigators. The 11th CIMT Annual Meeting will be held on May 14–16, 2013. Conflict of interest The authors declare that they have no conflict of interest. Cedrik Britten has been co-organizer of the meeting.

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