The “pan-cancer target” of TCR therapy was found
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The “pan-cancer target” of TCR therapy was found, and Bristol-Myers Squibb and GSK are expected to take advantage of it.
Despite the hype surrounding adoptive T-cell therapy in the biopharmaceutical industry in recent years, finding therapeutic targets that are consistent across tumor types and not expressed in healthy cells remains a challenge.
Recently, a team of scientists from the University of Pennsylvania, in collaboration with the immunotherapy drug development biotechnology company Immatics, has identified an antigenic component from 11 different solid tumor patient tissues, which is expected to provide a new breakthrough in the development of T cell therapy.
Immatics 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 fundamental to the company’s ability to collaborate with global leaders in the pharmaceutical industry in adoptive cell therapy and TCR bispecific drug development.
In a study published in the journal Science Translational Medicine, researchers report their discovery of a protein that slows the progression of cancer in mice when targeted by adoptive T-cell receptor (TCR) therapy.
The protein is 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 therapy.
Immatics now plans to conduct an investigational new drug application with the FDA with a view to initiating a Phase 1 clinical trial.
The team’s research goal 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 panel of normal and tumor tissue samples using Immatics’ XPRESIDENT discovery platform, which uses mass spectrometry to examine and compare hundreds of peptides in the panel of immune peptides, or a collection of peptides associated with human leukocyte antigens.
The XPRESIDENT analysis, combined with the company’s XCUBE bioinformatics approach, uses artificial intelligence to quantify the number of peptide copies in each cell.
Scientists have identified an antigenic component that is highly expressed in cancer cells of many types of tumors, but rarely expressed in human tissues: exons of type VI collagen VIα-3 or COL6A3 genes produced by tumors 6 Encoded epitope – a specific alternative splicing event that rarely occurs in healthy cells.
The COL6A3 protein, a component of type VI collagen, is present in connective tissues throughout the body, but exon 6 is only expressed in stromal cells in the tumor microenvironment.
Armed with a target, the researchers set out to develop TCRs that could 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.
Cancer growth slowed, and the mice did not experience serious side effects.
The results demonstrate that Immatics’ 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 application at the FDA, although the company did not provide a timeline.
As Immatics partners Genmab, GSK and Bristol-Myers Squibb are expected to continue to benefit from future cooperation projects.
In December 2021 , Bristol-Myers Squibb entered into a license agreement with Immatics to develop and commercialize Immatics’ TCR bispecific candidate IMA401.
Bristol-Myers Squibb paid an upfront payment of $150 million and development, regulatory and commercial milestone payments of up to $770 million for the exclusive worldwide license to IMA401.
It is worth mentioning that on January 25, 2022, the FDA approved Kimmtrak (Tebentafusp) for adult patients with HLA-A*02:01-positive unresectable or metastatic uveal melanoma (mUM). This is the first FDA-approved TCR-T therapy.
TCR-T cell therapy can target many antigens, and these antigens are expressed on and inside tumor cells.
Therefore, industry researchers believe that TCR-T is more suitable for solid tumors than CAR-T.
TCR-T is expected to become another popular cell therapy field after CAR-T!
References:
[1] Quantitative immunopeptidomics reveals a tumor stroma–specific target for T cell therapy, DOI: 10.1126/scitranslmed.abo6135
[2] Immatics official website (image source)
[3] www.fiercebiotech.com
The “pan-cancer target” of TCR therapy was found
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