Cell-based Immunotherapy

Immunotherapy is utilizing a patient’s own immune system to fight cancer as well as other diseases. Our immune system is capable of recognizing and eliminating cells that have become infected or damaged or become cancerous. Whereas radiation therapy or chemical therapy target the tumor itself, cancer immunotherapy focuses on boosting the activity of the immune system to erase the tumor. The strategies make use of the fact that many cancer cells express cancer antigens which can be detected by the immune system.

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The natural immune response may not be effective against tumors because a tumor may exploit several mechanisms to evade detection by the immune system: For example, the tumor may not express specific antigens or it has major histocompatibility complex (MHC) mutations, so that the immune system does not recognize the tumor. Or, the tumor may produce immune-suppressive molecules that inactivate the immune cells. Thus, boosting the immune response is used to overcome such evasive mechanisms.

In the early days, cancer immunotherapy mainly focused on immuno-stimulatory cytokine treatments. Cytokines, the intercellular signaling molecules of the immune system, can either exert a direct antitumor effect (e.g. TNF-α or Il-6) or indirectly enhance the antitumor immune response (e.g. IL-2 or IFN-α).

New cell-based immunotherapy approaches

More recent strategies focus on the increase of tumor-specific T cells, the most common treatments are antibody therapy, immune checkpoint inhibitors, cancer vaccines and cell-based immunotherapy.

Cell-based immunotherapy leverages immune cell types that are able to fight cancer due to their ability to bind to recognize and activate to kill cancer cells. Treatment regimens use a cell type from the immune system as therapeutic agent. For this purpose, the cells are first removed from the body, then activated or modified, expanded and finally re-infused into the patient.

Cell-based immunotherapies involve, but are not limited to, the following approaches:

Tumor-infiltrating lymphocyte (TIL) therapy

TIL therapy is a form of  adoptive cell therapy that harvests naturally occurring T cells that have already infiltrated patients’ tumors. These cells are then activated and expanded. Activated T cells are re-infused into patients, where they can then seek out and destroy tumors.

Engineered T-cell receptor therapy

Another type of adoptive therapy involves use of peripheral blood T cells genetically engineered ex vivo which express a cancer-specific T cell receptor (TCR). This approach involves taking T cells from patients, and an additional step of transfecting the cells with a new T cell receptor is performed. This enables them to target specific cancer antigens.

Chimeric Antigen Receptor (CAR)-T cell therapy

This CAR-T therapy is similar to other adoptive TIL therapies but is optimized even further as it involves arming a patient’s T cells via genetic engineering with a synthetic receptor known as a CAR, which stands for chimeric antigen receptor. A key advantage of CARs is their ability to bind to cancer cells even if their antigens are not presented on the surface via MHC making cancer cells more visible to the immune system for destruction.

Natural Killer (NK) cell therapy

NK therapy aims to activate innate immune responses. New areas of therapies being explored in the clinic involves equipping these NK cells with cancer-targeting CARs

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Dendritic Cell (DC) immune therapy

This strategy uses monocyte-derived dendritic cells that are antigen-presenting cells (APCs) to activate the immune system. To increase presentation of a tumor-specific antigen, DCs are pulsed ex vivo with tumor lysate or a specific cancer antigen, or genetically engineered to present the antigen. After re-infusion into the patient, the APCs activate the adaptive immune response via T lymphocytes.

While most cell-based approaches are still in the experimental phase compared to other cancer immunotherapy strategies, the first two adoptive T cell therapies have already been approved for the US, and partially approved for the EU market. Both products, Kymriah® from Novartis and Yescarta® from Gilead, are CAR-T cells targeting CD19 B-cell lymphomas.

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