On Demand Resources For CAR-T Discovery and Development Research

Following the success of the first checkpoint inhibitors for treating cancer, many researchers are now turning their attention to chimeric antigen receptor (CAR) T cell therapy. This novel treatment makes use of a cancer patient’s own T cells, which are removed and modified so that they can better recognize and attack cancer cells.

Topics to be covered:

• Diagnosing and managing CAR T cell therapy-related toxicities
• Identifying early predictive toxicity markers in patients treated with CAR T-cell therapy

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Cell therapy, especially adoptive T-cell transfer, is an active area of cancer research and treatment. Although promising, many challenges from efficacy to safety remain.   

Topics to be covered:

• Overview of gene-modulation technologies and functional genomic screens
•  Areas in which CRISPR-Cas9 and RNAi could be used to extend the use of adoptive T-cell transfer in the clinic

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The complexity of CAR-T therapy yields several challenges from discovery to development, however several solutions are emerging – giving scientists confidence in the safety, efficacy and integrity of these therapeutics.

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Since the 1990s, there have been clinical trials using genetically modified T cells. This has been possible due to advancements in gene delivery technology, allowing the creation of engineered T cells including chimeric antigen receptor (CAR)-T cell therapies and other novel therapeutic approaches, such as T cells resistant to HIV infection. 

Register now and watch the webinar by University of Pennsylvania's Dr. Bruce Levine to understand:

• The mechanism of action of CAR-T cells
• The clinical development from bench to bedside of a unique cell therapy
• The vein-to-vein complexities and healthcare challenges of developing a paradigm shift in therapies

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Understanding T cell biology and profiling new drugs or gene-based approaches that impact upon T cell activation pathways are critical for a broad spectrum of applications including drug discovery, adoptive cell therapy and enhanced understanding of autoimmune diseases.

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Cancers are the most heterogenous group of diseases affecting humans. Multiple compensating pathways work to promote disease progression. Various immunotherapies have shown anticancer promise, but the their targeted nature limits the scope of their action and applicability.

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Crossing the T and dotting the I of immunotherapy.
Welcome to Research Arc, a collection of Cell Press research hand-picked to advance your business. Research Arc helps you stay connected with the latest topics in therapeutic development programs, tapping into every stage of the translational continuum—from discovery to diagnostics.

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The recent FDA approval of the very first CAR-T therapy marks a significant milestone in the field of cell and gene therapy. However, this also hastens the need to streamline cell therapy workflows to make them more cost-effective, scalable, and safe, and to find solutions to replicate clinical success in solid tumors.

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Immunotherapies such as checkpoint inhibitors, CARTs and immune-targeting Abs have great promise for cancer treatment. Translational cell-based assays are required to optimize these approaches.

Here we describe image-based, immune cell-killing assays of 3D tumour spheroids, geared for assessing the efficacy of novel immune-modulators. Human tumour cell lines expressing RFP were used to form spheroids in 96-well ULA plates. Immune cells were then added and activated to kill. Spheroid viability was assessed over time (up to 10 days) by measuring the loss of RFP fluorescence using Incucyte^® live-cell analysis. 

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Monitoring the ex vivo activation of human T lymphocytes is key to developing an optimized and scalable adoptive cell therapy process. Described here is the development of a large-scale, multiplexed assay using high throughput flow cytometry to assess T-cell activation over time by combining immunophenotyping, cell proliferation, and cytokine profiling in a single assay.

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A critical process in bio-manufacturing of adoptive cell therapies such as chimeric antigen receptor (CAR) T and tumor infiltrating lymphocyte (TIL) therapies is the ex vivo expansion of T cells. Recent clinical studies show a correlation between ex vivo expansion and persistence of infused T cells and patient outcomes. Additional studies show that a subset of functional memory T cells including T memory stem cells (Tscm), central memory T cells (Tcm) and other less differentiated T cell subsets are responsible for long-term anti-tumor responses. This suggests that ex vivo T cell expansion protocols generating higher percentages of Tscm and Tcm in the total cell product are critical to significant clinical improvements in adoptive cell therapies.

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The blood cancers leukaemia, lymphoma and myeloma are expected to cause the deaths of > 55,000 people in the US in 2017. New immunological approaches afford great promise for improved therapies. Here, we describe novel high throughput live-cell image-based assays for immune cell activation and killing of blood cancer cells that are geared towards screening for new treatments for these malignancies. 

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Join a roundtable webinar reviewing the state-of-the-art in cell analysis and its specific utility in the CAR T cell therapy space as it seeks to advance beyond haematological malignancies and into the solid tumor space.

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Unprecedented advances in medicine are delivering remarkable results for some patients. Recent approvals of CAR T therapies and new approaches in regenerative medicine, for example, exemplify the progress being made. Much work remains, however, to extend the benefits of these game-changing treatment modalities to a larger patient population. Similarly, complex diseases such as Alzheimer’s and Parkinson’s, for which there are limited or no options for patients, continue to be the focus of research to drive discovery of new medicines.

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