Chordoma Foundation

Endogenous T cell therapy for chordoma

Amplifying the body’s natural immune response against chordoma

As a cancer forms, its cells accumulate genetic alterations that result in production of abnormal proteins not found in healthy cells. When our immune system detects one of these abnormal proteins, known as an “antigen,” it triggers production of T cells – essentially, the foot soldiers of the immune system – which are programmed to seek out and destroy any cells on which that antigen is found. Tumors form when cancer cells find ways to tamp down this T cell response, allowing them to multiply out of control.

Based on this understanding, much research over the past four decades has focused on finding ways to augment the body’s natural anti-cancer T cell arsenal so as to overpower and ultimately eliminate tumors. Several approaches have been developed to accomplish this – most notably Tumor Infiltrating Lymphocyte (TIL) therapy and Endogenous T Cell (ETC) therapy – which, in recent years, have generated dramatic responses in patients with a variety of tumor types. Both involve isolating anti-cancer T cells from a patient’s body, activating them and growing them up in large quantities in a laboratory, and then re-infusing them back into patients. ETC therapy, pioneered largely by Dr. Cassian Yee, has the advantage of utilizing T cells isolated directly from a patient’s blood rather than requiring a tumor biopsy.

Through this project, Dr. Yee and colleagues at The University of Texas MD Anderson Cancer Center are working to apply ETC therapy to chordoma through laboratory experiments intended to pave the way for an eventual ETC therapy clinical trial.

The translational phase of the project, which began in 2020 with support from a joint Chordoma Foundation – Cancer Research Institute grant, involves identifying chordoma-specific antigens, isolating T cells against these antigens from chordoma patients, and confirming the ability of these T cells to kill chordoma cells in chordoma cells and mouse models. If successful, this work will provide the understanding and preclinical proof of concept needed to initiate the first T cell therapy clinical trial for chordoma patients.

Why this project matters

Cell based therapies have demonstrated the ability to shrink or eliminate tumors of various types. In our assessment, applying these approaches to chordoma represents one of the most promising paths to better treatments and ultimately a cure. One of several cell based therapy approaches we are pursuing, ECT therapy is particularly attractive for its ability to be developed and tested in clinical trials faster than certain other forms of cell therapy; if successful, this project could lead to a clinical trial for chordoma patients within two to three years.

Investigators

Cassian Yee

Funding and support

The cost of the translational phase of this project is $200,000. If successful, additional funding will be required to evaluate ECT therapy in a clinical trial. 

Total funding provided to date: $200,000

Funding sources: $200,000 CLIP grant from CF and CRI | 07/20 – 07/22

Current funding need: $0

Strategic Initiative

Immunotherapy

Status

Ongoing

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