Interferon pathway genes regulate and predict efficacy of immunotherapy
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Publication Number
US-12662705-B2
Publication Date
2026-06-23
Expiration Date
Abstract
The present invention includes methods for treating cancer and selecting a patient for immunotherapy administration.
Core Innovation
The invention describes methods for treating cancer in a subject by measuring expression level of an interferon stimulating genes resistance signature (ISG.RS) metagene and measuring expression level of an interferon gene signature (IFNG.GS) metagene in a tumor and/or in a cancer cell or intratumoral immune cell. The method uses these measured expression levels as decision criteria to determine whether an immunotherapy comprising immune checkpoint blockade (ICB) is administered or whether an alternative cancer treatment is administered instead.
The decision is based on whether IFNG.GS exceeds ISG.RS or, in a ratio-based alternative, whether the IFNG.GS/ISG.RS ratio is increased relative to a reference sample. The approach is directed to melanoma treatment and ties patient selection to the relative balance between interferon gene signaling and an interferon stimulating genes resistance signature.
The invention further specifies melanoma metagene definitions for ISG.RS and IFNG.GS and supports optional inclusion of adoptive cell therapy such as CAR T cell therapy or TCR engineered T cell therapy as part of the immunotherapy. It also defines multiple modalities for measuring gene expression levels and eligible intratumoral immune cell types for measuring IFNG.GS.
Claims Coverage
The document provides two independent claims. Both claims center on selecting between immune checkpoint blockade (ICB) immunotherapy and an alternative cancer treatment based on interferon signature metagene measurements, with one claim using an IFNG.GS versus ISG.RS comparison and the other using an IFNG.GS/ISG.RS ratio versus a reference sample.
Metagene-guided ICB selection by IFNG.GS greater than ISG.RS
A method for treating cancer comprising measuring ISG.RS metagene expression level and measuring IFNG.GS metagene expression level in a tumor and/or a specified cancer cell or intratumoral immune cell, and administering immunotherapy comprising immune checkpoint blockade (ICB) when the measured IFNG.GS metagene expression level is greater than the measured ISG.RS metagene expression level, and otherwise administering an alternative cancer treatment when the measured ISG.RS metagene expression level is greater than the measured IFNG.GS metagene expression level, thereby treating the cancer.
Metagene ratio-guided ICB selection by increased IFNG.GS/ISG.RS versus reference
A method for treating cancer comprising measuring ISG.RS metagene expression level and measuring IFNG.GS metagene expression level in a tumor and/or an intratumoral immune cell, calculating a ratio of IFNG.GS over ISG.RS, administering immunotherapy comprising ICB when the ratio is increased in comparison to that of a reference sample, and administering an alternative cancer treatment when the ratio is not increased in comparison to that of a reference sample, thereby treating the cancer.
Claim coverage is driven by interferon signature metagene measurement and a rule for choosing ICB immunotherapy versus alternative cancer treatment. One independent claim uses a direct IFNG.GS versus ISG.RS comparison, while the other uses an IFNG.GS/ISG.RS ratio increased versus a reference sample. Both claims are grounded in specified melanoma metagene constituents and include dependent refinements on measurement samples, measurement modalities, and optional ICB and adoptive cell therapy configurations.
Stated Advantages
Enables treating cancer by selecting between immunotherapy comprising immune checkpoint blockade (ICB) and an alternative cancer treatment based on measured ISG.RS and IFNG.GS metagene expression relationships.
Documented Applications
Treating melanoma in a subject by measuring ISG.RS and IFNG.GS metagene expression levels and administering ICB immunotherapy when the specified IFNG.GS relationship is satisfied, or administering an alternative cancer treatment otherwise.
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