The Human Vaccines Project: A roadmap for cancer vaccine development

Romero, Pedro; Banchereau, Jacques; Bhardwaj, Nina; Cockett, Mark I.; Disis, Mary L.; Dranoff, Glenn; Gilboa, Eli; Hammond, Scott A.; Hershberg, Robert; Korman, Alan J.; Kvistborg, Pia; Melief, Cornelis J.M.; Mellman, Ira; Palucka, A. Karolina; Redchenko, Irina; Robins, Harlan; Sallusto, Federica; Schenkelberg, Theodore; Schoenberger, Stephen P.; Sosman, Jeffrey A.; Türeci, Özlem; Eynde, Benoı̂t Van den; Koff, Wayne C.; Coukos, George

doi:10.1126/scitranslmed.aaf0685

Cited by 160 publications

(112 citation statements)

References 70 publications

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“…However, as resistance to checkpoint blockade has become clinical reality and combination strategies are increasingly considered, there is a renewed interest in cancer vaccination (1,2). Cancer vaccines aim at inducing or restimulating tumor-specific T cell responses.…”

Section: Introductionmentioning

confidence: 99%

“…Cancer vaccines aim at inducing or restimulating tumor-specific T cell responses. Based on preclinical (1)(2)(3)(4)(5)(6)(7)(8)(9) and initial clinical reports (10)(11)(12), they could be instrumental in breaking primary resistance to checkpoint blockade of tumors with low mutational load (13)(14)(15) and in increasing response rates of highly mutated tumors, such as melanoma (11).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

Groß¹,

Erdmann²,

Haendle³

et al. 2017

JCI Insight

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

Groß¹,

Erdmann²,

Haendle³

et al. 2017

JCI Insight

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“…The majority of cancer vaccination trials have only provided partial results in the induction of an efficient anti-tumor cytotoxic T lymphocyte (CTL) response, due to the poor immunogenicity of antigenic peptides when administered alone, 17 suggesting the need for more powerful vaccines also in combination with standard chemotherapy 18-20 or with immune checkpoint inhibitory antibodies. 21-23 We have recently reported that patients receiving dacarbazine (DTIC) one day before peptide (Melan-A and gp100)-vaccination plus interferon (IFN)-α show a progressive enhancement of the TCR repertoire diversity of Melan-A-specific CD8 + T cells, accompanied by the maintenance of highly-avid and beneficial anti-tumor activity, as compared with cells isolated from patients receiving vaccination alone.…”

Section: Introductionmentioning

confidence: 99%

Antigen-specificity and DTIC before peptide-vaccination differently shape immune-checkpoint expression pattern, anti-tumor functionality and TCR repertoire in melanoma patients

et al. 2018

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We have recently described that DNA-damage inducing drug DTIC, administered before peptide (Melan-A and gp100)-vaccination, improves anti-tumor CD8+ Melan-A-specific T-cell functionality, enlarges the Melan-A+ TCR repertoire and impacts the overall survival of melanoma patients. To identify whether the two Ags employed in the vaccination differently shape the anti-tumor response, herein we have carried out a detailed analysis of phenotype, anti-tumor functionality and TCR repertoire in treatment-driven gp100-specific CD8+ T cells, in the same patients previously analyzed for Melan-A. We found that T-cell clones isolated from patients treated with vaccination alone possessed an Early/intermediate differentiated phenotype, whereas T cells isolated after DTIC plus vaccination were late-differentiated. Sequencing analysis of the TCRBV chains of 29 treatment-driven gp100-specific CD8+ T-cell clones revealed an oligoclonal TCR repertoire irrespective of the treatment schedule. The high anti-tumor activity observed in T cells isolated after chemo-immunotherapy was associated with low PD-1 expression. Differently, T-cell clones isolated after peptide-vaccination alone expressed a high level of PD-1, along with LAG-3 and TIM-3, and were neither tumor-reactive nor polyfunctional. Blockade of PD-1 reversed gp100-specific CD8+ T-cell dysfunctionality, confirming the direct role of this co-inhibitory molecule in suppressing anti-tumor activity, differently from what we have previously observed for Melan-A+CD8+ T cells, expressing PD-1 but highly functional. These findings indicate that the functional advantage induced by combined chemo-immunotherapy is determined by the tumor antigen nature, T-cell immune-checkpoints phenotype, TCR repertoire diversity and anti-tumor T-cell quality and highlights the importance of integrating these parameters to develop effective immunotherapeutic strategies.

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“…However, despite numerous studies, the efficacy of cancer vaccines remains inconclusive (55). Studies investigating neoantigens has prompted renewed excitement in the vaccine field (56).…”

Section: Pd-(l)1 Inhibitor Nonrespondersmentioning

confidence: 99%