Immunotherapy & CAR T Cells: Part 2

What challenges lie ahead for researchers working to develop and improve CAR-T therapies? Let’s explore!
👉Watch Part 1: https://youtu.be/ac_g0JDHejc
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Transcript:
- So, What's on the horizon for the CAR-T therapy field, and what challenges are researchers and clinicians going to tackle to enable the next success? We'll explore this exciting frontier in part two of our CAR-T video series.

If you find this video valuable, please take a second to like and subscribe. And if you are new to CAR-T technology, make sure to catch Part One for an orientation on how these therapies are designed. But if you're already up to speed, we'll dive right in.

Several open questions remain in this field, and are under active investigation. For example, how should different co-stimulatory signaling domains be selected to direct T cell fate? Which T cell subsets would work best in CAR-T therapy, in terms of proliferation, cytotoxicity, and durability?

To mitigate potential toxicities associated with CAR-T therapy, including cytokine release syndrome, neurotoxicity, and on-target/off-tumor toxicity, more research needs to be done to identify predictive biomarkers that could aid clinical monitoring and safety of future CAR-T therapies.

While CAR-T cells have shown much promise for the treatment of hematologic malignancies, leveraging this technology for the treatment of solid tumors has been much more challenging. Research is being done on the preclinical side to identify tumor antigens which are expressed homogeneously on tumor cells and not on normal, vital tissues, and to assess the risk for on-target/off-tumor toxicity.

The immunosuppressive tumor microenvironment poses another significant hurdle. Regulatory T cells, tumor associated macrophages, and myeloid derived suppressor cells can produce factors that dampen T cell activation. To mitigate these immunosuppressive effects, there is a strong desire to further engineer CAR-T cells or therapies to eliminate expression of T cell inhibitory molecules such as PD-1.

Another potential approach is to express cytokines and hybrid receptors to improve tumor infiltration and durability of response.

In its current state, CAR-T therapy must be customized to each patient, making it hard to achieve consistency and scalability. As a result, there is a strong desire to move toward allogeneic, or off-the-shelf, universal CAR-T therapy.

To this end, further genetic engineering of CAR-T cells is necessary to avoid host-versus-graft and graft-versus-host complications. This possibility has shown some promise in preclinical mouse models.

Many challenges lie ahead. Future CAR designs and cell engineering strategies should generate opportunities for improving precision of tumor targeting and T cell infiltration and migration to the solid tumor. In addition, future advances should improve control of CAR-T cell activation, proliferation, and persistence.

As CAR-T and other fields in immuno-oncology progress, CST is constantly expanding its portfolio of research-use antibodies for relevant targets. Our scientists have expertise in immune cell activation, cell death, and many more signaling pathways. Wherever your research takes you, we can work with you to identify the right targets for your studies. Get in touch with a scientist at https://cellsignal.com/support.

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#Immunotherapy #CART #Cancer #antibody

Видео Immunotherapy & CAR T Cells: Part 2 канала Cell Signaling Technology, Inc.