Meet the authors

TALK

Faster and More Predictive Immunotherapy Development with HUB Organoids

Speaker: Robert Vries, CEO, HUB Organoids 

Immunotherapy development is hampered by the lack of clinically relevant preclinical models, resulting in an enormous number of clinical trials, high attrition rates, and developmental costs. HUB Organoids are patient-derived in vitro models that recapitulate patient diversity and preserve tumor-specific antigens. Co-cultured with immune cells offers a scalable and predictive platform for immunotherapy development. Adopting HUB Organoids in immunotherapy development shortens the timelines for drug approval, allows for the identification of responders, and results in clinical candidates with a higher chance of success in patients.

POSTER PRESENTATION

Autologous Organoid-T cell co-culture platform as a powerful personalized model for Immuno-Oncology therapy

Authors: Soura Mardpour, Pleun Hombrink, Lorenz Jahn, Sylvia F. Boj, and, Farzin Pourfarza

HUB Organoids (HUB), Yalelaan 62, 3584CM, Utrecht, The Netherlands

Immunotherapy is a fast-developing and effective treatment strategy to combat cancer. New immuno-oncology (IO) modulators such as checkpoint inhibitors, and bispecific antibodies are increasingly populating the drug development pipelines, however, preclinical platforms that reliably model the tumor and immune cell interaction are still lacking. HUB Organoid Technology allows the development and in vitro expansion of patient-derived organoids (PDO) from normal and tumor patient tissues as three-dimensional primary cell cultures which retain the histological and mutational features of the original tumor tissue. Here we describe the development of “living” biobanks of patient-derived tumors and normal organoids matched with autologous immune cells from different epithelial organs, including but not limited to, the gastrointestinal tract and lungs. Additionally, we show the establishment of a co-culture platform based on colorectal cancer (CRC) PDO and their paired immune cells such as tumor-infiltrating lymphocytes (TIL).

POSTER PRESENTATION

Tumour organoid and T cell co-cultures to evaluate CAR-T cell cytotoxicity

Authors: Soura Mardpour¹; Mirella Georgouli²; Ana Pereira Puri²; Ravit Oren²; Joshua Audu-Evans²; Farzin Pourfarzad¹; Sylvia F Boj¹; Sara Brett² and Pleun Hombrink¹

¹HUB Organoids (HUB), Yalelaan 62, 3584CM, Utrecht, The Netherlands, ²GlaxoSmithKline (GSK), Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK

Recent advances in cancer immunotherapy had a positive impact on the life expectancy of patients for a large range of clinical indications. With new treatment strategies - such as engineered T cells - and druggable targets being identified at an increasing pace, the number of patients eligible for cancer immunotherapy is expected to expand steadily. However, promising therapeutic developments face hurdles in translating preclinical findings into therapy since conventional 2D cancer models hold low clinical predictive value. HUB developed an innovative alternative, building on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures when they are embedded into an extracellular matrix. Patient-specific organoids are generated from normal and malignant tissues and stored as biobanks with high quality and reproducibility. HUB Organoids® recapitulate complex characteristics of the original parental tissue, including molecular heterogeneity, and morphological and functional traits; and have been recently used to test the anti-cancer reactivity of engineered T cells. Since cancer progression and responses to immunotherapy are governed by immune cell interactions in the tumor microenvironment, we developed an assay in which CRC tumor organoids are co-cultured with T cells modified with chimeric antigen receptors (CAR-T cells) to assess their cytotoxic potential. CAR-T cell therapy has been demonstrated to be efficacious against many hematological malignancies, however therapeutic application to treat solid cancers remains challenging. Our organoid-T cell co-cultures offer a good platform to study the response of tumor organoids to CAR-T cells and will greatly contribute to our understanding of the critical factors that determine a successful CAR-T cell therapy.

POSTER PRESENTATION

Organoid co-cultures with autologous T cells to assess toxicity and efficacy of bispecific antibodies

Authors: Jahn L¹, Kempers M¹, Verkerk R¹, van DooremalenW¹, Steinacher L², Hombrink P¹, Lukovac S¹, Pourfarzad F¹, Cabon L², Boj SF¹

¹HUB Organoids (HUB), Utrecht, The Netherlands, ²Roche Pharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland

Cancer immunotherapy has positively impacted the life expectancy of patients for an extensive range of clinical indications. With new treatment strategies and druggable targets being identified at an increasing pace, the number of patients eligible for cancer immunotherapy is expected to expand steadily. However, conventionally used 2D cancer models lack the ability to translate preclinical findings into therapy and thereby sequester the progression of therapeutics with a clinical impact. HUB developed an innovative alternative, building on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures when embedded into an extracellular matrix. Patient-specific organoids are generated from normal and malignant tissues and stored as biobanks with high quality and reproducibility. HUB Organoids® recapitulate complex characteristics of the original parental tissue, including molecular heterogeneity and morphological and functional traits. Since cancer progression and responses to immunotherapy are governed by immune cell interactions in the tumor microenvironment, we developed an assay in which non-small cell lung cancer (NSCLC) organoids are co-cultured with autologous T cells to evaluate the activity and assess the cytotoxic potential of a bispecific antibody (TCB). Using our cocultures, we show T cell-mediated killing of tumor organoids expressing the TCB target antigen. PDO killing correlated with target antigen expression and bispecific antibody concentration. Our organoid-T cell co-cultures offer an excellent platform to study the response of tumor organoids to T cell bispecific antibodies and will significantly contribute to our understanding of the critical factors determining successful immunotherapies