Cell-Based Therapeutics Using Recombinant T Cell Receptor Genes

This invention presents a novel high-throughput screening method for isolating native, tumor-specific TCRs from single cells in a format in which they can be rapidly discovered, amplified, and returned to a patient on a timescale relevant for bedside therapy. While there has been significant progress in cancer immunotherapy, several limitations hinder new therapeutic development. Researchers at the University of Kansas have developed the first comprehensive sequence- and function-based annotation of epitope-specific T cell responses in patients, providing new molecular-scale technologies to guide the development of targeted cancer therapeutics.

Applications:

Immune-based cancer therapies have transformed clinical cancer treatment, and the role of CD8+ T-cells targeting tumor cells is particularly highlighted as a target for research. Adoptive immunotherapy is a promising form of immunotherapy in which autologous antigen-specific T-cells are expanded and modified ex vivo through genetic engineering and re-infused in the patient for tumor targeting.

How it works:

In this method, single T cells are encapsulated in micro compartments prior to physical linkage of their cDNA alpha and beta chain sequences. The linked alpha-beta TCR genes are cloned into their display platforms and screened for activity against cancer cells and viral agents. Newly discovered TCR genes are cloned into mammalian T-cells and returned to a patient as an antigen-specific cellular therapy.

Benefits:

This invention provides for rapid isolation of antigen-specific TCR libraries for development of personalized, targeted therapies for cancer and viral infections. The targeted therapies can be developed and administered more rapidly (in as few as five days to two weeks) than presently available cell-based therapies.

Why it is better:

A critical drawback of current immunotherapeutic strategies is that amplifyingglobalimmune responses can cause autoimmune responses and systemic side effects, such as skin rashes, liver toxicity, endocrinopathy, etc. Clinicians often must weaken dosages to alleviate such side effects. T-cell receptors (TCRs) responding to cancer cells are critical for cancer control. However, current TCR discovery platforms are slow, and most immunotherapeutic platforms activate/amplifyglobalimmune responses. This invention directly addresses these bottlenecks and allows for a targeted, personalized therapy that only amplifies tumor-specific autologous responses in the patient to enable better tumor targeting with minimal side-effects.

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