Champions Oncology’s AACR2024 Poster QuickTakes

Genomic DNA editing is a continuous process that occurs during the entire cell life span. The type and frequency of these modifications can be related to the physiological or pathological activity of intrinsic mechanisms such as DNA surveillance and repair or to extrinsic events that may induce an alteration of DNA sequence by exposure to agents that directly or indirectly induce accumulations of DNA alterations. In the past few years, large-scale analyses have revealed mutational signatures across human cancer types. These signatures can be used as markers of defective internal processes, such as DNA repair deficiency, or external exposures, such as carcinogens, like tobacco, or genotoxic therapies such as radiation and chemotherapy.

In this Poster QuickTake, we take a deep dive into evaluating mutational signatures in PDX models to give a better understanding of drug responses and companion biomarker identification.

Recent advances with engineered co-culture systems, such as microfluidic organ-on-chips, have overcome some of these limitations to better model cell-cell and cell-extracellular matrix (ECM) interactions. The microfluidic nature of these systems enables longer-term cell culture and allows for continuous effluent collection to monitor byproducts for tissue function and viability. They are also designed to recapitulate organ-level structure, function, and physical forces that mimic in vivo cyclic strain and fluid shear stress. Here, we use the Tumor-on-Chip (TOC) model to develop a complex co-culture system of our previously established TumorGraft3D (CTG3Ds) biobank at Champions Oncology.

In this Poster QuickTake, we take a deep dive into tumor-on-chip co-culture systems and their ability to investigate cancer progression.

There is a growing need to recreate a relevant tumor immune microenvironment (TIME) that is easily traceable to quickly delineate the effect of fine-tuning the different compartments.

Recent advances in Champions' TumorGraft3D (CTG3D) platform have not only generated robust models for preclinical drug evaluation but also elevated the translational relevance by efficiently mimicking the interactions between cancer organoids and immunocytes. Currently, available analytic approaches for coculture models are limited and are highly reliant on flow cytometry and high-resolution confocal imaging endpoints. These are often slow, cost-inefficient, and cloud computing heavy thereby limiting the bandwidth of studies and decision-making.

Easily traceable tags (e.g. bioluminescent and fluorescent) are attractive options that can aid the establishment of reliable effector (E) cells to the tumors (T) cell conditions, thus enabling the user to test multiple test agents cost-effectively and rapidly.

In this Poster QuickTake, we take a deep dive into the development of a bioluminescent 3D tumor platform with immune cell co-culture that can be utilized for high throughput screening.

Acute myeloid leukemia (AML) is the most common hematological malignancy found in acute leukemia patients. There is shown to be a strong genetic correlation to mechanisms of drug resistance/ sensitivity in AML. e.g.FMS-like tyrosine kinase 3 gene (FLT3) mutation occurs in about 30% of patients. In 2019, a phase 3 clinical trial suggested that gilteritinib treatment resulted in significantly longer survival than salvage chemotherapy in relapsed or refractory FLT3-mutated AML patients. Targeting FLT3-mutant (mut) in AML has become one of the important therapeutic strategies in this decade. Besides, TP53 mut, TET2 mut, and the overexpression of various drug-resistance genes were also reported as important biomarkers that impact the sensitivity of drug treatments.

Champions Oncology’s hematological VitroScreen platform provides user with a powerful and cost-friendly option to screen the performance of new FLT3 inhibitors or other novel anti-neoplastic test agents. In addition, the Lumin platform integrates Champions’ tumor model multi-omic data and public datasets in one accessible platform for model selection and data interpretation. We can apply the system biological method to categorize and design the test groups and predict the therapeutic outcome.

In this Poster QuickTake, we take a deep dive into the systemic analysis of gene mutations and therapeutic efficacy using the ex vivo hematological VitroScreen platform.

Acute Myeloid Leukemia (AML) is a highly heterogeneous disease with a diverse range of abnormal myeloid subpopulations resulting in challenges in clinical diagnosis and treatment. Many methods such as flow cytometry are used to provide precise information for risk stratification and treatment methods. Flow cytometry utilizes the expression patterns of cellular markers to characterize the high diversity in AML subpopulations with high sensitivity and specificity. This coupled with rapid analysis timelines allows for flow cytometry to be an excellent tool for the identification of AML lineage and progression through both phenotypic analysis and difference from normal. As AML lineage and disease progression are predictors of residual disease and relapse, the need for effective and accurate characterization of AML populations is critical.

In this Poster QuickTake, we take a deep dive into immunophenotyping using high-complexity flow cytometry in AML.

Acute myeloid leukemia (AML) poses a significant therapeutic challenge, with a rising incidence in recent times. This clonal hematopoietic disorder of progenitor and stem cells exhibits aggressive behavior, and despite initial remission, recurrence is common. The conventional shift from chemotherapy to monoclonal antibodies and antibody-drug conjugates (ADCs) has been hindered by the absence of AML-specific antigens. Notably, CD33, expressed strongly in 80–90% of AML cells, has become a target for gemtuzumab-ozogamicin (Mylotarg), the sole FDA-approved ADC for AML treatment.

While advancements in understanding AML molecular mechanisms have influenced clinical approaches, the lack of clinically representative models hinders therapeutic progress. Existing models, both in vivo and ex vivo, struggle to capture the heterogeneity and complexity of AML. Addressing this, we present our proprietary assay, Champions’ AML VitroScreen, designed for testing therapeutic candidates in primary AML samples. Our diverse bank of deeply characterized AML samples encompasses multiple subtypes, allowing the evaluation of therapeutic responses through cell viability, proliferation, and clonal composition analyses.

In this Poster QuickTake, we take a deep dive into the correlation between gemtuzumab-ozogamicin efficacy and CD33+ expression in AML primary samples using Champions' novel AML VitroScreen.

Fibroblasts can play a significant role in resistance to therapy. In the context of cancer cancer-associated fibroblasts (CAFs) in the TME have been associated with resistance to various therapeutic approaches. CAFs can contribute to therapy resistance through multiple mechanisms, including extracellular matrix remodeling, immune modulation, angiogenesis, and paracrine signaling. Understanding the intricate interactions between fibroblasts and cancer cells is crucial for developing more effective therapeutic strategies and overcoming resistance to cancer treatment.

In the pre-clinical stages of therapy testing, the use of clinically and biologically relevant models is essential. However, current preclinical tumor models often lack a comprehensive characterization of the TME. To address this limitation, Champions Oncology utilized transcriptomic data from its exclusive (TumorGraft) PDX models bank and analyzed the data with xCell computational method to identify molecular signatures predictive of fibroblast presence.

In this short AACR Poster QuickTake, we will take a deep dive into a novel gene signature that predicts fibroblast composition in the TME, allowing for an improved selection of PDX models for preclinical studies.