Abstract: The present invention provides a method for generating a biomarker signature for a subject with cancer. The method comprises calculating an intra-tumour heterogeneity measure and an inter-tumour heterogeneity measure for a plurality of genes. This is done using training data from a plurality of subjects who have had cancer, where the training data comprises gene expression data for a plurality of genes for each subject. A biomarker signature is generated by applying a heterogeneity filter to select genes having both an intra-tumour heterogeneity below an intra-tumour heterogeneity threshold and an inter-tumour heterogeneity above an inter-tumour heterogeneity threshold.

Abstract: Methods for determining the fraction of lymphocytes in a mixed sample comprising genomic material from multiple cell types are described. The methods comprise obtaining a read depth profile for the sample along a predetermined genomic region of interest including at least a portion of a genomic locus that undergoes VDJ recombination; obtaining a plurality of read depth ratios (ri) by normalising the read depths by reference to a baseline read depth derived from a subset of the region of interest; obtaining a summarised read depth ratio value (rVDJ) for a subset of the region of interest that is likely to be deleted through VDJ recombination; and determining the fraction of lymphocytes (f) in the sample as a function of the summarised read depth ratio value (rVDJ). Methods of providing a diagnosis or prognosis based on the lymphocyte fraction are also described, as well as related systems and products.

Abstract: The present invention provides a computer-implemented method for estimating the cancer cell fraction (CCF) of at least one tumour-specific mutation in a subject. Also provided are related methods for monitoring the clonal dynamics of a tumour, monitoring a treatment of the tumour and methods for treating a subject having a cancer, as well as systems for implementing the methods of the invention.

Abstract: The invention provides methods for detecting single nucleotide variants in lung cancer, especially stage 3a lung adenocarcinoma and lung squamous cell carcinoma. Additional methods and compositions, such as reaction mixtures and solid supports comprising clonal populations of nucleic acids, are provided.

Abstract: The present invention provides an engineered T cell for use in a method of treatment of a proliferative disorder, wherein the engineered T cell has modulated expression of one or more genes selected from SIT1, SAMSN1, SIRPG, CD7, CD82, FCRL3, IL1RAP, FURIN, STOM, AXL, E2F1, C5ORF30, CLDND1, COTL1, DUSP4, EPHA1, FABP5, GFI1, ITM2A, PARK7, PECAM1, PHLDA1, RAB27A, RBPJ, RGS1, RGS2, RNASEH2A, SUV39H1, and TNIP3. Further provided are activity modulators of one or more proteins encoded by genes selected from SIT1, SAMSN1, SIRPG, CD7, CD82, FCRL3, IL1RAP, FURIN, STOM, AXL, E2F1, C5ORF30, CLDND1, COTL1, DUSP4, EPHA1, FABP5, GFI1, ITM2A, PARK7, PECAM1, PHLDA1, RAB27A, RBPJ, RGS1, RGS2, RNASEH2A, SUV39H1, and TNIP3 for use in a method of enhancing immunotherapy in a subject having a proliferative disorder. Also provided are related methods of treatment employing the engineered T cell and/or inhibitor.

Abstract: The present invention relates to a method for determining whether an HLA allele is lost in a tumour in a subject, wherein said method comprises the step of determining the specific copy number of said HLA allele in said tumour. The invention also relates to a method for treating cancer in a subject, comprising targeting a neoantigen which is predicted to be presented by an HLA molecule encoded by an HLA allele which has been determined not to have been lost in a tumour in said subject.

Abstract: The present invention provides a method for providing a prognosis for a subject with lung cancer, the method comprising: (a) contacting a biological sample from the subject with reagents that specifically bind to each member of a panel of biomarkers comprising ANLN, ASPM, CDCA4, ERRFI1, FURIN, GOLGA8A, ITGA6, JAG1, LRP12, MAFF, MRPS17, PLK1, PNP, PPP1 R13L, PRKCA, PTTG1, PYGB, RPP25, SCPEP1, SLC46A3, SNX7, TPBG, XBP1; (b) determining a riskscore of the subject based on the nucleic acid levels of expression of the biomarkers in the samples; and (c) providing a prognosis for the lung cancer based on the risk score of the subject.

Abstract: The present invention relates to methods for identifying a subject with cancer who is suitable for treatment with an immune checkpoint intervention, and to methods of treatment of such subjects. The invention further relates to a method for predicting or determining the prognosis of a subject with cancer.

Abstract: The present invention relates to a method for determining whether an HLA allele is lost in a tumour in a subject, wherein said method comprises the step of determining the specific copy number of said HLA allele in said tumour. The invention also relates to a method for treating cancer in a subject, comprising targeting a neoantigen which is predicted to be presented by an HLA molecule encoded by an HLA allele which has been determined not to have been lost in a tumour in said subject.

Abstract: The present invention relates to a method for identifying a subject with cancer who is suitable for treatment with an immune checkpoint intervention, said method comprising analysing in a sample isolated from said subject the expressed frameshift indel mutational burden.

Abstract: The invention relates to subject-specific methods for detecting recurrence of tumours based on an understanding of the clonal/subclonal mutation profile of the subject's tumour and detection of the mutations in their cell-free DNA (cfDNA), typically by multiplex PCR of tumour mutations such as single nucleotide variants (SNVs).

Abstract: The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation.

Abstract: The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation.

Abstract: The invention provides methods for detecting single nucleotide variants in lung cancer, especially stage 3a lung adenocarcinoma and lung squamous cell carcinoma. Additional methods and compositions, such as reaction mixtures and solid supports comprising clonal populations of nucleic acids, are provided.

Abstract: The present invention relates to methods for identifying a subject with cancer who is suitable for treatment with an immune checkpoint intervention, and to methods of treatment of such subjects. The invention further relates to a method for predicting or determining the prognosis of a subject with cancer.

Abstract: The present invention relates to a method for identifying a truncal neo-antigen in a tumour from a subject which comprises the steps of: i) determining mutations present in a sample isolated from the tumour; and ii) identifying a truncal mutation which is a mutation present in essentially all tumour cells; and iii) identifying a truncal neo-antigen, which is an antigen encoded by a sequence which comprises the truncal mutation.