Oncology

Immuno- Oncology (IO) and CART Cell Therapeutics Evaluation Capabilities

Due to extensive immuno-oncology (IO) research, more effective and targeted treatment strategies for cancer have evolved in recent years. The approval and use of chimeric antigen receptor (CAR) T-Cell therapeutics in difficult-to-treat cancers has brought hope to millions of patients and oncologists globally. In particular, the success of CART-cell therapy in hematologic malignancies renewed efforts to use this technology against solid tumors as well. However, this strategy has had several challenges, including targeted delivery, penetration of therapeutics to tumor cells, immunogenicity, short- and long-term toxicity and safety, and efficacy of CART-cells in humans. To address the challenges above, several animal models have been utilized to screen potential CART-cell therapeutics as part of the IND-enabling process. 

In addition, bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to patient’s T cells and to tumor cells, inducing T-cell-mediated cytotoxicity of tumor cells. Humanized models with human peripheral mononuclear blood cells (PBMCs) in combination with a variety of xenograft models, are the most frequently used in-vivo platform for short-term screening of novel compounds. Full hematopoietic stem cell (CD34+) reconstituted models combined with genetically modified immunodeficient strains are utilized for long term screening of T-cell modulators, natural killer (NK) cell modulators, and other agents that induce antibody dependent cell cytotoxicity (ADCC), as well as various categories of immune checkpoint inhibitors and agonists.

Aragen Life Sciences is a leading R&D and manufacturing solutions provider for the life sciences industries worldwide offering end-to-end integrated and standalone solutions to advance small and large molecule programs from concept to commercialization. In vivo pharmacology services at Aragen offer specialized, customized, comprehensive portfolio of in vivo services for testing of your investigative immune-oncology cell therapeutics.

Why Aragen?

A team of experienced scientists and skilled in vivo research associates can support pre-clinical research from study design through execution as follows:

• Ensuring the successful intravenous adoptive transfer of CART-cells or human PBMCs into a mouse.
• Experience in performing in vivo CART therapeutic evaluations of both liquid and solid tumors.
  Figure 1. Representative study design for evaluating CART therapeutics
  
• Experience in using cryopreserved CART cells or human PBMCs with careful thawing and resuspension prior to the adoptive transfer (Harbani K. Malik-Chaudhry 2021).
• Experience in performing a wide range of cell line derived xenograft in humanized mouse models with successful identification of efficacy to support preparing IND program.
• Utilization of our bioluminescent imaging system to monitor tumor progressions in living animals.
  Figure 2. Ventral view images of mice after inoculation (6, 11 and 18 days) of Raji-Fluc cells both in non-humanized and humanized models.
   
  Top panel: raji-Luc disseminated, middle panel: raji-Luc in humanized model, and the bottom panel: raji-Luc treated with anticancer drug in the humanized model. The images were taken on days 6,8 and 11 post tumor cells implantation.
• Ex vivo supports including detection of tumor-specific or associated antigens on the surface of cancer cells by FACS, pre-screening of the PBMCs both in vitro or in vivo to reduce donor variability and to ensure consistency replicate studies by using the same donors, monitoring of CART cells in the host, and screening of human PBMCs engraftment.
  Figure 3. Engraftment of human PBMCs
  
  Bar graphs of CD45+ engraftment after hPBMC adoptive transfer. The leukocyte marker CD45+ and T-cell markers CD4+ and CD8+ measured from peripheral blood on 14, 18 and 21 days.

Our research facilities are in Morgan Hill, CA and we can accommodate same-day or second-day domestic shipping of your temperature-sensitive therapeutics and biological samples.

Validated IO Models

Case Studies:

Additional Models

• Lung metastasis model
• Orthotopic models of breast, kidney
• Subrenal capsule assay
• Vaccine model

Other Oncology Support

• In Vivo Bioluminescent Imaging
• 70+ cancer cell lines stored in-house to validate new models
• Pharmacokinetics and bioavailability of various test materials in tumour bearing mice
• Target engagement of compound in tumour tissue and PK/PD correlation
• MTD studies in immunocompromised mice

Aragen is a leading integrated discovery, development and manufacturing solutions provider for the global life sciences industry. Our Discovery Biology Services include In vitro and In vivo screening of new immunotherapies, including engineered chimeric antigen receptor (CAR)T-Cells (client provided) using translational animal models to support efficacy proof of concept studies in xenograft and syngeneic tumor models.

Typical readouts are, but not limited to:

• Immunophenotyping with multi-color FACS
• Cytokine panels
• ELISpot assays
• Multi gene analysis 
• Histology/ Immunohistochemistry 
• Protein/ peptide analytics

These services cater to a range of therapeutic areas including immuno-oncology research. 

In recent years, immuno-oncology research has made rapid progress, thanks to new therapeutic options such as CART-Cell. While the CART therapy is increasingly being used for treatment of human hematologic malignancies, there are several challenges including targeted delivery, immunogenicity and efficacy in solid tumors. 

To address these challenges and help you expedite your IO research projects to market, we have developed various mouse models to screen potential CART-cell therapeutics to support IND-enabling process.

The Aragen Advantage :

• Experienced and skilled team of in vivo research scientists to support pre-clinical research from study design through execution 
• Experience in intravenous transfer of CART-cells (or human PBMCs) into a mouse and in vivo / ex vivo CART therapeutic evaluations for liquid and solid tumors
• Experience in cell line derived xenograft- in humanized mouse models and non-invasive monitoring of tumor progressions in animals
• Detection of tumor-specific antigens by FACS, in vitro or in vivo pre-screening of the PBMCs and screening of human PBMCs
• Same/next day shipment of biological samples from our research facility at Morgan Hill, CA