The selection of appropriate preclinical models based on similarity to human biology and disease genotype and phenotype carries considerable potential to ensure higher predictability of preclinical trials. The design and interpretation of first-in-man
trials remains a major challenge in the development of novel anticancer agents. Key study design elements such as schedule, escalation strategy, targeted patient population, etc. rely heavily on preclinical (usually in vivo) data. This situation brings
into question the predictability of preclinical tumor models as well as the method of analysis and translation of the results of preclinical studies. It is especially difficult to model for preclinical assessment of cancer immunotherapy, the most
actively developing area in oncology. The need for stimulating the response of the immune system adds to the complexity of preclinical models and the applications. Cambridge Healthtech Institute’s Preclinical Models for Cancer Immunotherapy and Combinations conference aims to bring together cancer researchers and clinicians in order to initiate knowledge and opinion exchange around preclinical tumor models, including immunocompetent models, and the strategies for preclinical design and assessment of
cancer immunotherapy and combination therapy.
Day 1 | Day 2 | Download Brochure | Speaker Biographies
14 - 15 November: Preclinical Models for Cancer Immunotherapy and Combinations
15 - 16 November: Use of CRISPR & RNAi for Drug Discovery
14 November Dinner Short Course*: (SC1) Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy
15 November Dinner Short Course*: (SC3) Functional Screening Strategies Using CRISPR and RNAi
*Separate registration required.
Monday 14 November
7:30 Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
Michael Rugaard Jensen, Ph.D., Director, Head of ONC Discovery Pharmacology Basel, Novartis Institutes for BioMedical Research
8:30 Nonclinical Characterization of AMG 330, a CD3/CD33-Bispecific T-Cell-Engaging Antibody for the Treatment of Acute Myeloid Leukemia
Anja Henn, Ph.D., Scientist, Nonclinical Development, Amgen Research (Munich) GmbH
AMG 330 is a Bispecific T-cell engager (BiTE®) antibody construct binding to CD33 and CD3, which efficiently redirects cytotoxic T cells against CD33-expressing cells. In vitro and in vivo studies support clinical development of AMG 330 for the treatment of acute myeloid leukemia.
9:00 A Predictive in vitro Preclinical Package to Assess Safety and Efficacy of ImmTACs
Laure Humbert, Ph.D., Senior Scientist, Preclinical Biology, Immunocore Ltd.
ImmTACs are bispecific molecules comprising a pico-molar affinity T cell receptor fused to an anti-CD3 specific scFv that re-direct a potent T cell response towards target cells. Here we present our in vitro approach
for preclinical assessment. This entirely in vitro package is used to evaluate safety and efficacy of ImmTACs. The predictability of this process for our most advanced molecule IMCgp100 currently in a Phase I/II study
is discussed.
9:30 Immunotherapy for Head and Neck Cancer: Using T-Cells to Drive Away the Tumour
Marc Davies, Ph.D., CAR Mechanics Laboratory, Research Oncology, Division of Cancer Studies, King’s College London
To treat refractory squamous cell carcinoma of the head and neck (SCCHN), we have engineered tumour-specific T-cells through expression of a Chimeric Antigen Receptor (CAR) that targets the extended ErbB family. Efficacy and safety of this approach were
confirmed using several in vitro and in vivo models. A Phase I clinical evaluation is now ongoing in patients with locally advanced/recurrent SCCHN in whom CAR T-cells are delivered
using the intra-tumoural route.
10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Immunocompetent Mouse Models as a Tool for Cancer Immunotherapy Pipeline Advancement
Christian Gerdes, Ph.D., Head of Pharmacology, Roche Pharma Research & Early
Development, Roche
As immunotherapy gains more and more traction, the need for more predictive preclinical models grows as well. It is widely recognized that immunocompetent mice are used to assess the anti-tumor efficacy of cancer immunotherapies. This presentation will
discuss the uses of mouse models and how they can advance drug pipelines.
11:15 Mouse Clinical Trials: Large Scale in vivo Screening Predicts Drug Response in Cancer Patients
Michael Rugaard Jensen, Ph.D., Director, Head of ONC Discovery
Pharmacology Basel, Novartis Institutes for BioMedical Research
We established a panel of more than 1,000 patient-derived tumor xenograft models (PDX), with comprehensive genomic landscape analyses. Using this PDX collection, we performed population-based in vivo compound screens
using a 1x1x1 experimental design to assess the response and resistance of 70 treatments across six indications. We demonstrate both the reproducibility and clinical translatability of this approach and additionally demonstrate examples of PDX superiority
over cell-based xenografts in predicting clinical response.
11:45 Preclinical Assessment of Immune Checkpoint Inhibitors and Their Combinations: IDO1 Inhibitor Case Study
Gregory Driessens, Ph.D., Head of in vivo Pharmacology, iTeos Therapeutics
SA
Tumors use tryptophan-catabolizing enzymes like IDO1 to induce an immunosuppressive microenvironment. PF-06840003 is a new highly selective orally bioavailable IDO1 inhibitor able to reverse IDO1-induced T-cell anergy in vitro.
PF-06840003 reduced intratumoral kynurenine and inhibited tumor growth in multiple preclinical syngeneic models, in combination with immune-checkpoint inhibitors. PF-06840003 has favorable predicted human pharmacokinetic properties, including a predicted
t1/2 of 16-19 hours, highlighting its strong potential as a clinical candidate in Immuno-Oncology.
12:15 NHP & Humanized Models for Efficacy Evaluation of Ab Drugs & Immunotherapies
Jia
Zeng, Ph.D., Director, Scientific Product Development Pharmacology, PharmaLegacy Laboratories Co., Ltd
Non-human Primate (NHP) and humanized models are good preclinical efficacy test systems for both antibody and immune therapies. PharmaLegacy (PL) has established efficacy-test platforms with a range of NHP models in many disease areas. Meanwhile, PL is developing novel models with humanized immune system for testing immunotherapy. PL’s NHP platforms have evaluated many candidate mAb drugs targeting molecules like TNFα/IL-6/IL-1β and RANKL/Sclerostin, and helped dozens of clients with IND filing to both FDA and CFDA.
12:45 Enjoy Lunch on Your Own
13:15 Session Break
14:15 Chairperson’s Remarks
Christian Gerdes, Ph.D., Head of Pharmacology, Roche Pharma Research & Early Development, Roche
14:20 KEYNOTE PRESENTATION:
Stress, Death, Immunity and Cancer Therapy
Lorenzo Galluzzi, Ph.D., Université Paris Descartes
Some anticancer agents trigger a form of cell death that can elicit an adaptive immune response. Such an “immunogenic cell death” relies on the activation of key stress responses in dying cells, and the consequent emission of danger signals
that alert the organism of a threat. Unfortunately, this process is frequently suboptimal, calling for combinatorial strategies that attempt to restore the full-blown immunogenicity of cell death for therapeutic purposes.
14:50 Applying Preclinical Immuno-Oncology Mouse Models to Guide Combination Strategies in the Clinic
Elaine M. Pinheiro, Ph.D., Principle Scientist, In Vivo Pharmacology, Immuno-Oncology,
MSD, Merck
Immunotherapeutic strategies, such as checkpoint blockade, have changed the way cancers are being treated, providing significant benefit to patients. Despite success, a large fraction of patients do not respond to single agent therapy. Combination approaches
may be the key to improving response rates in these patients. Preclinical immuno-oncology mouse models provide tremendous value to shaping clinical strategies given that countless potential combinations exist with other immunotherapies, radiation,
and/or standard of care. In turn, data from clinical trials can be used to formulate hypothesis about biological mechanisms that can be appropriately and productively tested in preclinical models to drive the development of novel immunotherapeutic
approaches and combination strategies. This talk will provide an overview of the limitations, predictive nature, and role of these models in guiding treatment options at the bedside.
15:20 PANEL DISCUSSION: Increasing Predictability of Preclinical Trials in Oncology and Immuno-Oncology
Moderator:
Christian Gerdes, Ph.D., Head of Pharmacology, Roche Pharma
Research & Early Development, Roche
Panelists: Speakers of the Day
Topics to Be Discussed:
- In vivo modeling of anti-tumor immune response
- Leveraging phenotypic features of models to minimize translational failures
- Modeling for preclinical assessment of combination cancer therapy
- Integrating in vitro and in vivo pharmacology approaches
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:30 Interactive Breakout Discussion Groups
Topic: Preclinical Design of Combination Cancer Therapy
Moderator:
Michael Rugaard Jensen, Ph.D., Director,
Head of ONC Discovery, Pharmacology Basel, Novartis Institutes for BioMedical Research
- Understanding the intersection of critical signaling pathways
- Combining without eroding therapeutic index
- Overcoming tumor heterogeneity
- Translatability to the clinic
Topic: Organoid Models and Next Generation Drug Development
Moderator:
Sylvia Boj, Ph.D., Group Leader, Foundation Hubrecht Organoid Technology (HUB Foundation)
- Proving genetic and phenotypic stability
- Benefits for preclinical testing and drug screening
- Implications for personalized medicine
Topic: Targeting Cancer with Genome Editing
Moderator:
Dieter Saur, Professor of Molecular Biology, Technical University of Munich
- Creating next generation models
- Generating an inducible dual-recombinase system by combining Flp/frt and Cre/loxP
- Next steps with Crispr/ Cas9
17:30 Welcome Reception in the Exhibit Hall with Poster Viewing
18:30 Close of Day
19:00 – 21:30 Recommended Dinner Short Course*
(SC1) Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy
* Separate registration required
Day 1 | Day 2 | Download Brochure |
Speaker Biographies
Tuesday 15 November
7:00 Registration and Morning Coffee
8:25 Chairperson’s Remarks
Christine Sedlik, Ph.D., Institut Curie
8:30 Preclinical Development of Humanized Mouse Models to Evaluate Cancer Immunotherapies
Christine Sedlik, Ph.D., Institut Curie
To improve our understanding and to build better, more translatable in vivo mouse tumor models, we are focusing on the development of humanized mouse models consisting of the transplant of patient-derived tumor xenografts
(available at Institut Curie) into immunodeficient mice reconstituted with human immune cells (isolated from the matching patient from the draining lymph nodes or with allogenic PBMCs).
9:00 Use of Juvenile Animal Studies as a Preclinical Model to Support Oncology Medicine Development in Children
Dinah Duarte, Pharm.D., MSc, Head, Scientific Evaluation Unit, Directorate of Medicinal
Products, INFARMED, Portugal
Childhood cancer has remained a challenge because of long-term effects in children. The need to extend children’s access into new cancer therapies requires early prediction of safety aspects and juvenile animal studies (JAS) are being conducted
to screen for age-related toxicities and differences occurring during postnatal development. The retrospective review of the oncology EU medicines and Paediatric Investigation Plans is illustrative of the potential significance of JAS in oncology
medicines.
9:30Enhancing Immunotherapy Radiotherapy Combinations Using the Small Animal Radiation Research Platform
Andrew Lessey, Business Development Specialist, Xstrahl Limited
The synergistic effect of combining Immunotherapeutic agents with radiotherapy has been employed to great success in some instances within the clinic. However, the benefits of trialling these combinations in a preclinical setting has been routinely
been examined in a very crude manner or ignored until the clinic thus far. We have developed the SARRP to allow researchers to accurately examine these combinations in small animal models.
9:45 Selected Poster Presentations
Tumour Regression Following Inhibition of Different Signalling Pathways in DEN-Induced Hepatocarcinogenesis in C57BL/6 Mice
Alex Giakoustidis, M.D., Ph.D., Senior Clinical Fellow in HPB Surgery, Hammersmith Hospital at Imperial College Healthcare NHS Trust
Investigating a Naturally Occurring Small Molecule, EBC-46, as an Immunotherapeutic Agent to Help Treat Cancer
Jason K. Cullen, Ph.D., Research Officer, QIMR Berghofer
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Patient-Derived Tumour Organoids for Drug Screening and Development
Sylvia Boj, Ph.D., Group Leader, Foundation Hubrecht Organoid Technology (HUB Foundation)
Organoid 3D growth systems were devised for studying the role of adult stem cell function and cell differentiation. The organoid models essentially contribute an in vitro mini organ setting that allows the expansion
of normal and tumour patient-derived cells. The generation of ‘Living Organoid Biobanks’ from cancer patients will provide a valuable platform for drug development. The possible value of organoids for predicting therapy responses for
patients is currently being assessed.
11:15 Modelling and Targeting Pancreatic Cancer and Its Microenvironment by Genome Engineering and Gene Editing in Mice
Dieter Saur, M.D., Consultant and Senior Group Leader, Technische Universität München
(TUM), School of Medicine
We generated novel PDAC models that permit spatial and temporal control of gene expression and modelling of PDAC subtypes. These tools provides unparalleled access to the native biology of cancer cells and their hosting stroma, and rigorous genetic
validation of candidate therapeutic targets in autochtonous tumours and the immune system.
11:45 Generation of ex vivo Tumor Models from PDX Tumors as a Platform for Clinically Relevant Anticancer Drug Discovery
Geoffrey A. Bartholomeusz, Ph.D., Associate Professor
and Director, siRNA Core Facility, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Monolayer cell cultures platforms inadequately represent the complex tumor microenvironment and drugs identified by these systems have failed when translated into the clinics. Clinically relevant PDX systems are both costly and time consuming.
We have developed a clinically relevant ex-vivo tumor tissue system derived from PDX tumor and preliminary data confirms its potential to serve as a platform for clinically relevant drug discovery in a time and cost effective manner.
12:15 End of Conference
Day 1 | Day 2 | Download Brochure | Speaker Biographies