Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer

Guo, Zengqing; Yuan, Yuan; Chen, Chao; Lin, Jing; Ma, Qiwang; Li, Geng; Gao, Yan; Huang, Ying; Chen, Ling; Chen, Lizhu; Huang, Yu-Fang; Wang, Hailun; Li, Bo; Chen, Yu; Zhang, Xi

doi:10.1038/s41698-022-00279-3

Cited by 36 publications

(27 citation statements)

References 43 publications

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“…Neoantigen-loaded DC vaccines can expand the antigenic breadth and clonal diversity of anti-tumor immunity. 9,112,[356][357][358][359][360][361] Several clinical trials are investigating the efficacy and safety of personalized neoantigen DC vaccines in solid tumors, such as melanoma, bladder cancer, colorectal cancer, esophageal cancer, breast cancer, ovarian cancer, pancreatic cancer, hepatocellular carcinoma, lung cancer, and gastric cancer (Table 4).…”

Section: Nucleic Acid Vaccinesmentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

254

150

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Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

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Section: Nucleic Acid Vaccinesmentioning

confidence: 99%

Neoantigens: promising targets for cancer therapy

Xie

Shen

Gao

et al. 2023

Sig Transduct Target Ther

254

150

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“…Consequently, we used WT1 protein for antigen pulsing. The most widely studied approach in DC therapy uses mo-DC pulsed with WT1 in conjunction with chemotherapy [ 12 ]. The safety and immunogenicity of mo-DC has been confirmed through clinical trials [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mo-DC are primarily involved in inflammation and promote TH17 immune response [ 10 ] ( Figure 1 A). Currently, mo-DC is most used in the field of DC anti-cancer immunotherapy research [ 11 , 12 , 13 ]. Although mo-DC is well-tolerated and safe, low therapeutic efficacy has hindered its widespread use.…”

Section: Introductionmentioning

confidence: 99%

WT1 Pulsed Human CD141+ Dendritic Cell Vaccine Has High Potential in Solid Tumor-Targeted Immunotherapy

Cho

Jeong

Jeon

et al. 2023

IJMS

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Dendritic cells (DC) are powerful cells that play critical roles in anti-tumor immunity, and their use in cancer immunotherapy unlocks hidden capabilities as an effective therapeutic. In order to maximize the full potential of DC, we developed a DC vaccine named CellgramDC-WT1 (CDW). CDW was pulsed with WT1, an antigen commonly expressed in solid tumors, and induced with zoledronate to aid DC maturation. Although our previous study focused on using Rg3 as an inducer of DC maturation, problems with quality control and access led us to choose zoledronate as a better alternative. Furthermore, CDW secreted IL-12 and IFN-γ, which induced the differentiation of naïve T cells to active CD8+ T cells and elicited cytotoxic T lymphocyte (CTL) response against cancer cells with WT1 antigens. By confirming the identity and function of CDW, we believe CDW is an improved DC vaccine and holds promising potential in the field of cancer immunotherapy.

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“…Moreover, the patients with metastatic gastric cancer have received the administration of neoantigen-pulsed DC (Neo-MoDC) vaccines combined with immune checkpoint inhibition (ICI). Although the Neo-MoDC vaccine alone could trigger neoantigen-specific CD4 + and CD8 + TCRs, the combination therapy induced a higher immune response and significant elimination of tumors ( 68 ). Notably, a phase Ib trial (CHUV-DO-0017_PC-PEPDC_2017) was also conducted on a DC vaccine pulsed with personalized neoantigen peptides (PEP-DC) coupled with the treatment of chemotherapy and the anti-PD-1 antibody.…”

Section: Neoantigen-based Dendritic Cell Vaccines In Pancreatic Cancermentioning

confidence: 99%

Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer

Zhang

Dai

et al. 2023

Front. Immunol.

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The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous mutations in the tumor cell genome will produce non-autologous proteins (neoantigen) to activate the immune system by activating CD4+ and CD8+ T cells. Neoantigen-based peptide vaccines have exhibited exciting therapeutic effects in treating various cancers alone or in combination with other therapeutic strategies. Furthermore, antigen-loaded DC vaccines are more powerful in inducing stronger immune responses than vaccines generated by antigens and adjuvants. Therefore, neoantigen-based dendritic cell (DC) vaccines could achieve promising effects in combating some malignant tumors. In this review, we summarized and discussed the recent research progresses of the neoantigen, neoantigen-based vaccines, and DC-based vaccine in pancreatic cancers (PCs). The combination of the neoantigen and DC-based vaccine in PC was also highlighted. Therefore, our work will provide more detailed evidence and novel opinions to promote the development of a personalized neoantigen-based DC vaccine for PC.

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Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer

Cited by 36 publications

References 43 publications

Neoantigens: promising targets for cancer therapy

Neoantigens: promising targets for cancer therapy

WT1 Pulsed Human CD141+ Dendritic Cell Vaccine Has High Potential in Solid Tumor-Targeted Immunotherapy

Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer

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