New targets for pan-cancer, new directions for medicine!
In recent years, despite the hype surrounding adoptive T-cell therapies in the biopharmaceutical industry, it remains a challenge to find therapeutic targets that are consistent across different tumor types and are not expressed in healthy cells. Recently, a team of scientists from the University of Pennsylvania and immunotherapy drug development biotechnology company Immatics have identified an antigen component from 11 different solid tumor patient tissues, which is expected to provide new breakthroughs in the development of T cell therapies.
In recent years, despite the hype surrounding adoptive T-cell therapies in the biopharmaceutical industry, it remains a challenge to find therapeutic targets that are consistent across different tumor types and are not expressed in healthy cells.
Recently, a team of scientists from the University of Pennsylvania and immunotherapy drug development biotechnology company Immatics have identified an antigen component from 11 different solid tumor patient tissues, which is expected to provide new breakthroughs in the development of T cell therapies.
Immatics company combines the discovery of true targets for cancer immunotherapy with the development of the right T cell receptors, with the goal of achieving robust and specific T cell responses against these targets. This deep expertise is the foundation for the company's ability to collaborate with global leaders in the pharmaceutical industry for adoptive cell therapies and TCR bispecific drug development.
In a study published in the journal Science Translational Medicine, researchers report their discovery of a protein that, when targeted by adoptive T-cell receptor (TCR) therapy, slows the growth of cancer in mice. The protein is highly prevalent in tumor samples from patients with 11 different types of solid tumors, but is rarely present in healthy cells, making it a major potential target for T-cell therapies.
Immatics now plans to pursue an investigational new drug application with the FDA with a view to initiating a Phase 1 clinical trial. The goal of the team's research is to find antigens present in different tumor types that can be safely used in T cell therapy without harming other cells. The researchers first analyzed a set of normal and tumor tissue samples using Immatics's XPRESIDENT discovery platform, which uses mass spectrometry to examine and compare hundreds of peptides in immune peptide groups, or a collection of peptides associated with human leukocyte antigen XPRESIDENT analysis, combined with the company's XCUBE bioinformatics approach, using artificial intelligence to quantify the number of peptide copies per cell.
The scientists identified an antigenic component that is highly expressed in cancer cells of many types of tumors, but rarely expressed in human tissues: an epitope encoded by tumor-producing type VI collagen VIα-3 or exon 6 of the COL6A3 gene-a specific alternative splicing event that rarely occurs in healthy cells. COL6A3 protein, a component of collagen type VI, is present in connective tissue throughout the body, but exon 6 is expressed only in stromal cells of the tumor microenvironment.
With the goal in mind, the researchers set out to develop TCRs that can recognize epitopes without attacking other peptides. Again using data from the Immatics Discovery Platform to compare reactivity between tumor and normal cells, the team developed high-affinity TCR-T cells and injected them into mice that had been transplanted with human leukemia cells. The growth of the cancer slowed and the mice did not develop serious side effects.
The results demonstrate that Immatics's XPRESIDENT approach can be used not only to identify potential therapeutic targets, but also to develop TCRs with robust safety profiles.
Next, Immatics plans to conduct more research on the COL6A3 epitope to support its IND filing with the FDA, although the company did not provide a timeline. As Immatics company partners Genmab, GSK and BrifyMyers Squibb are expected to continue to benefit from future cooperation projects.
In December 2021, Bristol-Myers entered into a licensing agreement with Immatics to develop and commercialize Immatics's TCR bispecific candidate project, IMA401. Bristol-Myers Squibb pays $0.15 billion upfront and up to $0.77 billion in development, regulatory and commercial milestone payments for the exclusive worldwide license to IMA401. It is worth mentioning that on January 25, 2022, the FDA approved Kimmtrak(Tebentafusp) for use in adults with unresectable or metastatic uveal melanoma (mUM) who were HLA-A * 02:01 positive. This is the first FDA-approved TCR-T therapy. TCR-T cell therapy can target many antigens, and these antigens are expressed on the surface and inside of tumor cells. Therefore, industry researchers believe that TCR-T is more suitable for solid tumors than CAR-T. TCR-T is expected to become after CAR-T, another hot cell therapy field!