Innovative Personalized Medicine Platform that Recapitulates the Human Immune System for the Development of Novel Oncology Therapeutics

Summary

• It is well known that individual cancers’ behavior and therapeutic response can not be accurately reproduced by traditional tumor models
• Better models that can recapitulate patient specific responses are desperately needed in order to understand why certain therapies work for some people and not for others
• Dr. Inghirami is a KOL in developing humanized cancer models
• Dr. Inghirami has developed a novel platform that allows for patient specific murine cancer models
• These models can be used to better understand patient specific tumors, evaluate response to treatment, and create a comprehensive biobank of real tumor samples

Technical Overview

• Patient-Derived Tumor Xenograft (PDTX) models have revol-utionized cancer research by recapitulating human tumors in mice
• Dr. Inghirami has developed a novel state-of-the-art platform in which PDTX models are co-implanted with patient tumor cells and an autologous/allogenic hematopoietic/immunologic system, creating a patient-specific murine humanized immuno-oncologic PDTX (Hi-PDTX)

The platform provides several key competitive advantages:

• A global understanding of the immunological changes of host elements in response to autologous tumor cells
• Informative tools to study tumor evolution and resistance, assess clonal expansion and antigen recognition of host elements
• Better clinical prediction to both conventional and new drugs allowing for the design of personalized therapies
• Ability to test a variety of modalities, including novel antibody-based therapeutics and engineered effector elements (i.e., CAR-T and CAR-NK, etc.), by allowing lead candidate activities and toxicities to be assessed in a humanized environment

Market Opportunity

• Patient-specific factors and the tumor microenvironment may contribute to varying levels of efficacy in clinical trials and clinical practice of approved drugs
• Dr. Inghirami’s Hi-PDTX platform enables a 360º view of patient-specific tumors
• The platform allows for a highly cost-effective and timesaving approach to the development of novel therapeutics
• This precision medicine approach will not only lead to the identification of novel therapeutics, but it will also enable the optimization of existing treatment options
• The ability to identify novel biomarkers predictive of clinical outcome and/or linked to changes posed by therapeutic interventions

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep domain expertise and a strong presence in oncology to advance the development of this platform and deploy it to identify novel cancer therapeutics

Supporting Data / Figures

Figure 1: Hi-PDTX models. Ex-vivo expanded adult CD34 HSC will be implanted into pre-conditioned immunocompromised mice. Full
reconstitution (>70% human cells with the peripheral blood) will be then randomized to receive vehicle of PDTX cells. Mice will be followed overtime to assess tumor grafts, PFS and OS will be used as primary endpoints. Samples (i.e., blood and organs) will be used to study host-tumor interaction suing a panel of platforms. Lastly, to test therapeutic strategies, control (PDTX) and Hi-PDTX mice will be challenged with single of multi-drug combinations or immune effector cells.