HLA class I-restricted <i>MYD88</i> L265P-derived peptides as specific targets for lymphoma immunotherapy

Nelde, Annika; Walz, Juliane S.; Kowalewski, Daniel J.; Wolz, Olaf Oliver; Peper, Janet Kerstin; Gloria, Yamel Cardona; Langerak, Anton W.; Muggen, Alice F.; Claus, Rainer; Bonzheim, Irina; Fend, Falko; Salih, Helmut R.; Kanz, Lothar; Rammensee, Hans Georg; Stevanović, Stefan; Weber, Alexander N.R.

doi:10.1080/2162402x.2016.1219825

Cited by 32 publications

(25 citation statements)

References 61 publications

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“…Rosenberg's team identified time in which the T cells were stimulated by antigens in vitro are a key factor affecting the immune responses. For instance, T cell responses observed after several approximately 3-week rounds of stimulations based on artificial APCs or irradiated APCs were confirmed to be mediated by de novo-primed naive T cells rather than by preexisting memory T cells, as short-time stimulation of the same PBMCs did not result in the detection of specific T cell clones (28)(29)(30). In this study, the neoantigen identification was based on the detection of spontaneous memory T cell responses, which may be more suitable for refractory advanced solid tumors with very short survival time: (a) A therapeutic vaccine for preexisting antigen-specific T cells, which were produced as a secondary immune response after vaccination, was more rapid and more intense.…”

Section: Discussionmentioning

confidence: 97%

Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors

Chen¹,

Zou²,

Du³

et al. 2019

Journal of Clinical Investigation

177

162

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METHODS. Two different pipelines of neoantigen identification were established in this study: (a) Clinical-grade targeted sequencing was performed in patients with refractory solid tumor, and mutant peptides with high variant allele frequency and predicted high HLA-binding affinity were synthesized de novo. (b) An inventory-shared neoantigen peptide library of common solid tumors was constructed, and patients' hotspot mutations were matched to the neoantigen peptide library. The candidate neoepitopes were identified by recalling memory T cell responses in vitro. Subsequently, neoantigen-loaded dendritic cell vaccines and neoantigen-reactive T cells were generated for personalized immunotherapy in 6 patients. RESULTS. Immunogenic neoepitopes were recognized by autologous T cells in 3 of 4 patients who used the de novo synthesis mode and in 6 of 13 patients who used the shared neoantigen peptide library. A metastatic thymoma patient achieved a complete and durable response beyond 29 months after treatment. Immune-related partial response was observed in another patient with metastatic pancreatic cancer. The remaining 4 patients achieved prolonged stabilization of disease with a median progression-free survival of 8.6 months. CONCLUSION. The current study provides feasible pipelines for neoantigen identification. Implementing these strategies to individually tailor neoantigens could facilitate neoantigen-based translational immunotherapy research.

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Section: Discussionmentioning

confidence: 97%

Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors

Chen¹,

Zou²,

Du³

et al. 2019

Journal of Clinical Investigation

177

162

View full text Add to dashboard Cite

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“…Tumor-specific neoepitopes can derive from protein-alteration mutational events. Nelde et al have identified a set of HLA class 1 MyD88 L265P-derived ligands that elicit specific T cell responses [28]. These data highlight the potential of MyD88 L265P-mutation-specific peptides-based immunotherapy as a novel personalized treatment approach.…”

Section: Tlr Inhibitorsmentioning

confidence: 98%

How Recent Advances in Biology of Waldenström’s Macroglobulinemia May Affect Therapy Strategy

et al. 2019

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Purpose of Review Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder. Up to now, therapeutic choice was not influenced by the biological characteristics of the disease. Here, we will review how recent advances in biology in WM may affect therapy strategy. Recent Findings Recently, WM has been described as a new oncogenic model. MyD88 mutation has been described as a key driver mutation and has functional consequences which could be targeted. Other mutations, such as CXCR4 or TP53, have been reported. These mutations are associated with different clinical presentation, prognosis, and treatment response. Summary Mutational status may influence therapeutic choice in some patients but additional data are required. New targeted therapies are on development.

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“…However, it is difficult to detect neoantigens in cancer cells with a low mutation load, although neoantigens also occur (38,39), but in this condition, this method cannot distinguish them from normal peptides. In addition, most neoantigens are unique to one special patient, although there are some neoantigens, such as the MYD88 L265P mutation, the histone 3 variant H3.3 K27M mutation, and the KRAS G12D hotspot-driver mutation, that are present in several patients (40)(41)(42). Even in the same cancer entity, the distribution of neoantigens is heterogeneous, which hinders the application of single anti-cancer drugs and creates an intractable problem in cancer treatment.…”

Section: Obstacles To This Strategymentioning

confidence: 99%

“…As MYD88 L265P is a widely occurring and tumor-specific mutation in NHL, Nelde et al predicted potential MYD88 L265P -containing HLA ligands for several HLA class I restrictions in silico. Three HLA-B * 07restricted peptides and one HLA-B * 15-restricted peptide were identified, and they found that MYD88 L265P -derived peptides can induce mutation-specific and functional immune responses in vitro (41).…”

Section: Myd88 Mutantmentioning

confidence: 99%

Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

2020

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Adoptive cell therapy (ACT) is a kind of immunotherapy in which T cells are genetically modified to express a chimeric antigen receptor (CAR) or T cell receptor (TCR), and ACT has made a great difference in treating multiple types of tumors. ACT is not perfect, and it can be followed by severe side effects, which hampers the application of ACT in clinical trials. One of the most promising methods to minimize side effects is to endow adoptive T cells with the ability to target neoantigens, which are specific to tumor cells. With the development of antigen screening technologies, more methods can be applied to discover neoantigens in cancer cells, such as whole-exome sequencing combined with mass spectrometry, neoantigen screening through an inventory-shared neoantigen peptide library, and neoantigen discovery via trogocytosis. In this review, we focus on the side effects of existing antigens and their solutions, illustrate the strategies of finding neoantigens in CART and TCR-T therapies through methods reported by other researchers, and summarize the clinical behavior of these neoantigens.

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HLA class I-restricted MYD88 L265P-derived peptides as specific targets for lymphoma immunotherapy

Cited by 32 publications

References 61 publications

Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors

Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors

How Recent Advances in Biology of Waldenström’s Macroglobulinemia May Affect Therapy Strategy

Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

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