Trial Watch: Peptide-based anticancer vaccines

Bloy, Norma; Buqué, Aitziber; Eggermont, Alexander M.M.; Cremer, Isabelle; Sautès-Fridman, Catheriné; Galon, Jérôme; Tartour, Éric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

doi:10.4161/2162402x.2014.974411

Cited by 100 publications

(86 citation statements)

References 255 publications

(223 reference statements)

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“…A number of therapeutic peptide-vaccination protocols have been developed to induce CD8 + T cell responses against the tumor by administering antigenic peptides expressed by cancer cells combined with adjuvants. 1 , 2 Hence, the need to identify relevant peptides eliciting efficient T-cell responses and specific CD8 + T-cell receptor (TCR) repertoire, able to recognize and eliminate tumor cells. 1 , 3 A critical determinant is to study the TCR-MHC complex in terms of affinity/avidity, and its impact on T-cell differentiation, survival, persistence as well as tumor reactivity.…”

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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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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“…Since the publication of the last Trial Watch dealing with this topic (April 2015), 118 the results of no less than 20 clinical trials testing peptide-based vaccination as a therapeutic approach in cancer patients have reported in the peer-reviewed literature (source https://www.ncbi.nlm.nih.gov/pubmed and http://meetinglibrary.asco.org/abstracts). Most of these trials were Phase I or II studies designed for testing the safety and immunogenicity (as opposed to the therapeutic efficacy) of TAA-derived peptides.…”

Section: Literature Updatementioning

confidence: 99%

“…Since the last Trial Watch dealing with peptide-based vaccines for oncological indications has been published (April 2015), 118 no less than 66 clinical trials have been initiated to test this immunotherapeutic modality in cancer patients (source www.clinicaltrials.gov) (Table 1). A large majority of these studies involve either short TAA-derived peptides that can directly bind to MHC Class I or II molecules expressed by antigen-presenting cells 176 (42 studies), or SLPs that are processed intracellularly and then loaded on MHC Class I or II molecules 172,177,178 (22 studies), most often in combination with immunological adjuvants 179-182 like montanide ISA-51 (water-in-oil emulsion) 181,183 Hiltonol® (poly- L -lysine in carboxymethylcellulose, a TLR3 ligand) 184 and GM-CSF.…”

Section: Ongoing Clinical Trialsmentioning

confidence: 99%

“…Although final statistical assessments are still awaited, preliminary results from 8 clinical trials that have been completed or terminated since the publication of our last Trial Watch dealing with peptide-based anticancer vaccines (April 2015) 118 have become available (source www.clinicaltrials.gov). NCT01423760, an open-label, common safety follow-up trial testing a MUC1-targeting vaccine (tecemotide) in patients with myeloma and NSCLC has been terminated prematurely as per decision of the sponsor.…”

Section: Ongoing Clinical Trialsmentioning

confidence: 99%

“…111-116 Thus, besides a few exceptions and despite promising preclinical findings, 117 multiple studies demonstrate that peptide-based vaccines employed as standalone adjuvanted interventions have limited clinical activity (although they generally cause some signs of tumor-targeting immunity). 118-121 In line with this notion, no peptide-based vaccines are currently approved by the US Food and Drug Administration (FDA) or equivalent agencies worldwide for use in cancer patients are therapeutic measures (source http://www.fda.gov). However, on 2017, July 10th, the FDA has granted Orphan Drug Designation (ODD), which is designed to encourage the preparation of new molecules for indications affecting fewer than 200,000 people in the US, to DSP-7888, a new peptide-based vaccine targeting Wilms tumor 1 (WT1).…”

Section: Introductionmentioning

confidence: 99%

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Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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At the bench: Engineering the next generation of cancer vaccines

Shae

Baljon

Wehbe

et al. 2019

Journal of Leukocyte Biology

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Cancer vaccines hold promise as an immunotherapeutic modality based on their potential to generate tumor antigen-specific T cell responses and long-lived antitumor responses capable of combating metastatic disease and recurrence. However, cancer vaccines have historically failed to deliver significant therapeutic benefit in the clinic, which we maintain is due in part to drug delivery challenges that have limited vaccine immunogenicity and efficacy. In this review, we examine some of the known and putative failure mechanisms of common first-generation clinical cancer vaccines, and describe how the rational design of materials engineered for vaccine delivery and immunomodulation can address these shortcomings. First, we outline vaccine design principles for augmenting cellular immunity to tumor antigens and describe how well-engineered materials can improve vaccine efficacy, highlighting recent innovations in vaccine delivery technology that are primed for integration into neoantigen vaccine development pipelines. We also discuss the importance of sequencing, timing, and kinetics in mounting effective immune responses to cancer vaccines, and highlight examples of materials that potentiate antitumor immunity through spatiotemporal control of immunomodulation. Furthermore, we describe several engineering strategies for improving outcomes of in situ cancer vaccines, which leverage local, intratumoral delivery to stimulate systemic immunity. Finally, we highlight recent innovations leveraging nanotechnology for increasing the immunogenicity of the tumor microenvironment (TME), which is critical to enhancing tumor infiltration and function of T cells elicited in response to cancer vaccines. These immunoengineering strategies and tools complement ongoing advances in cancer vaccines as they reemerge as an important component of the immunotherapeutic armamentarium.

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Trial Watch: Peptide-based anticancer vaccines

Abstract: Equally contributed to this work.z Share senior co-authorship.

Cited by 100 publications

References 255 publications

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

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

Trial watch: Peptide-based vaccines in anticancer therapy

At the bench: Engineering the next generation of cancer vaccines

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