Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies

Rähni, Annika; Jaago, Mariliis; Sadam, Helle; Pupina, Nadežda; Pihlak, Arno; Tuvikene, Jürgen; Annuk, Margus; Mägi, Agnes; Timmusk, Tõnis; Ghaemmaghami, Amir M.; Palm, Kaia

doi:10.1038/s43856-022-00114-7

Cited by 5 publications

(4 citation statements)

References 68 publications

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“…Interestingly, melanocyte-derived antigens like MLANA, TYR and PMEL are stably expressed across our selected UM samples. 20 Moreover, TMEM200C has been recently identified as a potential marker for progression in UM. 21 To further avoid peptide cross-reactivity, we first extracted all overlapping k-mer peptides of length 9-12 for all proteins expressed from the 22 prioritized genes.…”

Section: Antigen and Peptide Selection To Minimize The Risk Of Iraementioning

confidence: 99%

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy

Lischer,

Eberhardt,

Flamann

et al. 2024

J Immunother Cancer

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BackgroundTumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers.MethodsWe present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach. In addition to minimizing the risk of immune-related adverse events by selecting antigens based on their expression profile in tumor biopsies and healthy tissues, we incorporated a network analysis-derived antigen indispensability index based on computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model relying on peptide physicochemical characteristics.ResultsIn a model study of uveal melanoma, Human Leukocyte Antigen (HLA) docking simulations and experimental quantification of the peptide–major histocompatibility complex binding affinities confirmed that our approach discriminates between high-binding and low-binding affinity peptides with a performance similar to that of established methodologies. Blinded validation experiments with autologous T-cells yielded peptide stimulation-induced interferon-γ secretion and cytotoxic activity despite high interdonor variability. Dissecting the score contribution of the tested antigens revealed that peptides with the potential to induce cytotoxicity but unsuitable due to potential tissue damage or instability of expression were properly discarded by the computational pipeline.ConclusionsIn this study, we demonstrate the feasibility of the de novo computational selection of antigens with the capacity to induce an anti-tumor immune response and a predicted low risk of tissue damage. On translation to the clinic, our pipeline supports fast turn-around validation, for example, for adoptive T-cell transfer preparations, in both generalized and personalized antigen-directed immunotherapy settings.

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Section: Antigen and Peptide Selection To Minimize The Risk Of Iraementioning

confidence: 99%

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy

Lischer,

Eberhardt,

Flamann

et al. 2024

J Immunother Cancer

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“…Immunization using pC89hisP1A phages has resulted in the generation of Th1-dominated immune responses and has prolonged the survival of mice challenged with P815F3 cells [ 183 ]. Next-generation phage-display mimotope variation analysis has identified antibody responses to targeted cancer therapies, revealing melanoma-associated and cancer-testis antigens linked to DC vaccines and anti-PD-1 monoclonal antibodies [ 184 ].…”

Section: Revolutionary Strategy Of Engineered Bacteriophages For Comb...mentioning

confidence: 99%

Engineered Phage-Based Cancer Vaccines: Current Advances and Future Directions

Ragothaman

Yoo

2023

Vaccines

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Bacteriophages have emerged as versatile tools in the field of bioengineering, with enormous potential in tissue engineering, vaccine development, and immunotherapy. The genetic makeup of phages can be harnessed for the development of novel DNA vaccines and antigen display systems, as they can provide a highly organized and repetitive presentation of antigens to immune cells. Bacteriophages have opened new possibilities for the targeting of specific molecular determinants of cancer cells. Phages can be used as anticancer agents and carriers of imaging molecules and therapeutics. In this review, we explored the role of bacteriophages and bacteriophage engineering in targeted cancer therapy. The question of how the engineered bacteriophages can interact with the biological and immunological systems is emphasized to comprehend the underlying mechanism of phage use in cancer immunotherapy. The effectiveness of phage display technology in identifying high-affinity ligands for substrates, such as cancer cells and tumor-associated molecules, and the emerging field of phage engineering and its potential in the development of effective cancer treatments are discussed. We also highlight phage usage in clinical trials as well as the related patents. This review provides a new insight into engineered phage-based cancer vaccines.

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“…5,32 Melanoma TILs are enriched for specificity for melanoma-associated antigens (MAGEs), which include cancer-testis antigens (CTAs) and neo-antigens, which carry unique self-antigen epitopes. Neo-antigens are formed from tumor somatic mutations and contribute to tumor immunogenicity, 36,37 on which immunotherapeutic therapies are based.…”

Section: Reviewmentioning

confidence: 99%

Understanding the Complexities of Melanoma Immunobiology and a Review of Immunotherapeutic Checkpoint Inhibito

Kituashvili,

Urushadze

2023

Georgian Biomedical News

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Melanoma immunotherapy has emerged as a promising treatment approach for advanced melanoma, a lethal form of skin cancer. Despite the remarkable clinical outcomes observed with immune checkpoint inhibitors, melanoma still poses significant therapeutic challenges. In this review, we discuss the immune landscape of melanoma, including the interactions between tumor cells and immune cells in the tumor microenvironment, according to the latest research studies. We also cover the immunobiology of melanoma and the mechanisms by which melanoma can evade immunosurveillance. Additionally, the review highlights emerging immunotherapeutic strategies that can overcome these mechanisms, including combination therapies and the use of novel agents that target immune checkpoints, their efficacy, and potential adverse effects. The goal of this timely review is to provide an up-to-date understanding of the complex interplay between melanoma and the immune system, and to identify new opportunities for developing effective melanoma immunotherapies.

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Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies

Cited by 5 publications

References 68 publications

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy

Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy

Engineered Phage-Based Cancer Vaccines: Current Advances and Future Directions

Understanding the Complexities of Melanoma Immunobiology and a Review of Immunotherapeutic Checkpoint Inhibito

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