Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma

Hu, Zhuting; Leet, Donna; Allesøe, Rosa Lundbye; Oliveira, Giacomo; Li, Shuqiang; Luoma, Adrienne; Liu, Jinyan; Forman, Juliet; Huang, Teddy; Iorgulescu, J. Bryan; Holden, Rebecca L.; Sarkizova, Siranush; Gohil, Satyen; Redd, Robert A.; Sun, Jing; Elagina, Liudmila; Giobbie‐Hurder, Anita; Zhang, Wandi; Peter, Lauren; Ciantra, Zoe; Rodig, Scott J.; Olive, Oriol; Shetty, Keerthi S.; Pyrdol, Jason W.; Uduman, Mohamed; Lee, Patrick; Bachireddy, Pavan; Buchbinder, Elizabeth I.; Yoon, Charles H.; Neuberg, Donna; Pentelute, Bradley L.; Hacohen, Nir; Livak, Kenneth J.; Shukla, Sachet A.; Olsen, Lars Rønn; Barouch, Dan H.; Wucherpfennig, Kai W.; Fritsch, Edward F.; Keskin, Derin B.; Wu, Catherine J.; Ott, Patrick A.

doi:10.1038/s41591-020-01206-4

Cited by 287 publications

(230 citation statements)

References 45 publications

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“…The eight patients' average growth time was as long as 4 years, and six showed no signs of disease. [ 28 ]…”

Section: The Selection Of Suitable Antigens and Adjuvantsmentioning

confidence: 99%

Development of Effective Tumor Vaccine Strategies Based on Immune Response Cascade Reactions

Zhai

et al. 2021

Adv Healthcare Materials

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To solve the problems of high toxicity and poor efficacy of existing tumor treatment methods, researchers have developed a variety of tumor immunotherapies. Among them, tumor vaccines activate antigen‐presenting cells and T lymphocytes upstream of the cancer‐immunity cycle are considered the most promising therapy to activate the immune system. Nanocarriers are considered the most promising tumor vaccine delivery vehicles, including polymer nanocarriers, lipid nanocarriers, inorganic nanocarriers, and biomimetic nanocarriers that have been developed for vaccine delivery. Based on the cascade reaction for tumor vaccines to exert their effects, this review summarizes the four key factors for the design and construction of nano‐tumor vaccines. The composition and functional characteristics of the corresponding preferred nanocarriers are illustrated to provide a reference for the development of effective tumor vaccines. Finally, potential challenges and perspectives are illustrated in the hope of improving the efficacy of tumor vaccine immunotherapy and accelerating the clinical transformation of next‐generation tumor vaccines.

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“…The eight patients' average growth time was as long as 4 years, and six showed no signs of disease. [ 28 ]…”

Section: The Selection Of Suitable Antigens and Adjuvantsmentioning

confidence: 99%

Development of Effective Tumor Vaccine Strategies Based on Immune Response Cascade Reactions

Zhai

et al. 2021

Adv Healthcare Materials

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“…NeoVax is a peptide-based, personalized neoantigen-based vaccine tested in a phase 1 trial with four patients with previous history of high-risk stage III and two patients with stage IV melanoma after initial surgical resection [ 148 ]. The NeoVax vaccine is constructed with 20 different long peptides (15–30 mers) and administered with adjuvant poly ICLC (TLR3 agonist consisting of carboxymethyl cellulose, polyinosine-polycytidyl acid and poly l-lysine double-stranded RNA).…”

Section: Combination Therapies With Icismentioning

confidence: 99%

Combining Cancer Vaccines with Immunotherapy: Establishing a New Immunological Approach

Kim

Sang

Lee

et al. 2021

IJMS

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Therapeutic cancer vaccines have become increasingly qualified for use in personalized cancer immunotherapy. A deeper understanding of tumor immunology and novel antigen delivery technologies has assisted in optimizing vaccine design. Therapeutic cancer vaccines aim to establish long-lasting immunological memory against tumor cells, thereby leading to effective tumor regression and minimizing non-specific or adverse events. However, due to several resistance mechanisms, significant challenges remain to be solved in order to achieve these goals. In this review, we describe our current understanding with respect to the use of the antigen repertoire in vaccine platform development. We also summarize various intrinsic and extrinsic resistance mechanisms behind the failure of cancer vaccine development in the past. Finally, we suggest a strategy that combines immune checkpoint inhibitors to enhance the efficacy of cancer vaccines.

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“…One was treated with surgical resection, and two developed metastatic diseases. The researchers observed that in all eight patients, 28–59 months after vaccination, 68% of the specific CD4 T-cell responses and 59% of the epitope-specific CD8 T-cell responses recorded at week 16 remained detectable, indicating a persistent immune response [ 37 ].…”

Section: Second-generation Combination Therapymentioning

confidence: 99%

Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy

2021

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Effective treatment of established tumors requires rational multicombination immunotherapy strategies designed to target all functions of the patient immune system and tumor immune microenvironment. While these combinations build on the foundation of successful immune checkpoint blockade antibodies, it is increasingly apparent that successful immunotherapy will also require a cancer vaccine backbone to engage the immune system, thereby ensuring that additional immuno-oncology agents will engage a tumor-specific immune response. This review summarizes ongoing clinical trials built upon the backbone of cancer vaccines and focusing on those clinical trials that utilize multicombination (3+) immuno-oncology agents. We examine combining cancer vaccines with multiple checkpoint blockade antibodies, novel multifunctional molecules, adoptive cell therapy and immune system agonists. These combinations and those yet to enter the clinic represent the future of cancer immunotherapy. With a cancer vaccine backbone, we are confident that current and coming generations of rationally designed multicombination immunotherapy can result in effective therapy of established tumors.

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Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma

Cited by 287 publications

References 45 publications

Development of Effective Tumor Vaccine Strategies Based on Immune Response Cascade Reactions

Development of Effective Tumor Vaccine Strategies Based on Immune Response Cascade Reactions

Combining Cancer Vaccines with Immunotherapy: Establishing a New Immunological Approach

Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy

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