Mining the Immunopeptidome for Antigenic Peptides in Cancer

León‐Letelier, Ricardo A.; Katayama, Hiroyuki; Hanash, Sam

doi:10.3390/cancers14204968

Cited by 12 publications

(4 citation statements)

References 120 publications

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“…This may pose limitations to MAPPs analyses as compound-derived peptides containing PTMs occurred in our study, usually oxidation at methionine or de-amidation of asparagine and glutamine, and researchers are highlighting the importance of epitope PTMs in immunopeptidomes. Notably, Katayama et al [ 67 ] discovered that MHC-II-bound citrullinated peptides are a source of immunogenicity, and León-Letelier et al [ 68 ] asserts that PTMs can induce immunogenicity more than their unmodified counterparts.…”

Section: Discussionmentioning

confidence: 99%

Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved Predictability of Potential T Cell Epitopes

Hartman,

Steiner,

Siegel

et al. 2023

Biology

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A critical step in the immunogenicity cascade is attributed to human leukocyte antigen (HLA) II presentation triggering T cell immune responses. The liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based major histocompatibility complex (MHC) II-associated peptide proteomics (MAPPs) assay is implemented during preclinical risk assessments to identify biotherapeutic-derived T cell epitopes. Although studies indicate that HLA-DP and HLA-DQ alleles are linked to immunogenicity, most MAPPs studies are restricted to using HLA-DR as the dominant HLA II genotype due to the lack of well-characterized immunoprecipitating antibodies. Here, we address this issue by testing various commercially available clones of MHC-II pan (CR3/43, WR18, and Tü39), HLA-DP (B7/21), and HLA-DQ (SPV-L3 and 1a3) antibodies in the MAPPs assay, and characterizing identified peptides according to binding specificity. Our results reveal that HLA II receptor-precipitating reagents with similar reported specificities differ based on clonality and that MHC-II pan antibodies do not entirely exhibit pan-specific tendencies. Since no individual antibody clone is able to recover the complete HLA II peptide repertoire, we recommend a mixed strategy of clones L243, WR18, and SPV-L3 in a single immunoprecipitation step for more robust compound-specific peptide detection. Ultimately, our optimized MAPPs strategy improves the predictability and additional identification of T cell epitopes in immunogenicity risk assessments.

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Section: Discussionmentioning

confidence: 99%

Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved Predictability of Potential T Cell Epitopes

Hartman,

Steiner,

Siegel

et al. 2023

Biology

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“…These TAAs are targets of endogenous immunity, epigenetically regulated, and associated with poor outcomes. 40 These non-canonical peptides are present on ~16% of major histocompatibility complex (MHC) I in cancer cells. 41 One promising strategy is to include both overexpressed proteins and non-canonical peptides in a cancer vaccine to induce a stronger immune response.…”

Section: Prevention Vaccines For Non-virally Induced Cancersmentioning

confidence: 99%

Advances and challenges in cancer immunoprevention and immune interception

Stanton,

Castle,

Finn

et al. 2024

J Immunother Cancer

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Invasive cancers typically evade immune surveillance through profound local and systemic immunosuppression, preventing their elimination or control. Targeting immune interventions to prevent or intercept premalignant lesions, before significant immune dysregulation has occurred, may be a more successful strategy. The field of cancer immune interception and prevention is nascent, and the scientific community has been slow to embrace this potentially most rational approach to reducing the global burden of cancer. This may change due to recent promising advances in cancer immunoprevention including the use of vaccines for the prevention of viral cancers, the use of cancer-associated antigen vaccines in the setting of precancers, and the development of cancer-preventative vaccines for high-risk individuals who are healthy but carry cancer-associated heritable genetic mutations. Furthermore, there is increasing recognition of the importance of cancer prevention and interception by national cancer organizations. The National Cancer Institute (NCI) recently released the National Cancer Plan, which includes cancer prevention among the top priorities of the institute. The NCI’s Division of Cancer Prevention has been introducing new funding opportunities for scientists with an interest in the field of cancer prevention: The Cancer Prevention-Interception Targeted Agent Discovery Program and The Cancer Immunoprevention Network. Moreover, the Human Tumor Atlas Network is spearheading the development of a precancer atlas to better understand the biology of pre-invasive changes, including the tissue microenvironment and the underlying genetics that drive carcinogenesis. These data will inform the development of novel immunoprevention/immuno-interception strategies. International cancer foundations have also started recognizing immunoprevention and immune interception with the American Association for Cancer Research, Cancer Research UK and the Society for Immunotherapy of Cancer each implementing programming focused on this area. This review will present recent advances, opportunities, and challenges in the emerging field of cancer immune prevention and immune interception.

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“…This information is particularly useful to select cell panels for in vitro studies, as many characterized cell lines are available from cell repositories, like ATCC 4 and ECACC 5 . MS data of pHLA complexes is continually expanding and immunopeptidome databases catalog actual pHLA complexes that can also be considered in antigen selection ( 65 , 66 ).…”

Section: Module 1: Target Antigen Selectionmentioning

confidence: 99%

Evolution by innovation as a driving force to improve TCR-T therapies

Schendel

2023

Front. Oncol.

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Adoptive cell therapies continually evolve through science-based innovation. Specialized innovations for TCR-T therapies are described here that are embedded in an End-to-End Platform for TCR-T Therapy Development which aims to provide solutions for key unmet patient needs by addressing challenges of TCR-T therapy, including selection of target antigens and suitable T cell receptors, generation of TCR-T therapies that provide long term, durable efficacy and safety and development of efficient and scalable production of patient-specific (personalized) TCR-T therapy for solid tumors. Multiple, combinable, innovative technologies are used in a systematic and sequential manner in the development of TCR-T therapies. One group of technologies encompasses product enhancements that enable TCR-T therapies to be safer, more specific and more effective. The second group of technologies addresses development optimization that supports discovery and development processes for TCR-T therapies to be performed more quickly, with higher quality and greater efficiency. Each module incorporates innovations layered onto basic technologies common to the field of immunology. An active approach of “evolution by innovation” supports the overall goal to develop best-in-class TCR-T therapies for treatment of patients with solid cancer.

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Mining the Immunopeptidome for Antigenic Peptides in Cancer

Cited by 12 publications

References 120 publications

Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved Predictability of Potential T Cell Epitopes

Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved Predictability of Potential T Cell Epitopes

Advances and challenges in cancer immunoprevention and immune interception

Evolution by innovation as a driving force to improve TCR-T therapies

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