Trial watch: Peptide-based vaccines in anticancer therapy

Abstract

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

An agonistic anti‐Toll‐like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy

“…46 The IFN-c produced by Ag-specific CD8 T-cells in OVA/anti-TLR4 mAb-immunized mice may have induced H-2K b in B16F10 tumour cells in vivo. 17 However, peptide-vaccine therapy has failed to show clinical efficacy, despite its safety and tolerability in patients with cancer. Indeed, B16F10 tumours can be eradicated by cytotoxic CD8 T-cells in vivo.…”

“…This possibility suggests that OVA/anti-TLR4 mAb therapy may be effective against some MHC I-negative tumours. [15][16][17]35 Thus, most tumour Ags expressed exclusively or preferentially by tumours, but not normal tissues, are likely not suitable targets for tumour vaccine therapy. 46 Whereas EG7 and MC38 cells secrete OVA extracellularly, B16F10 cells retain OVA intracellularly because the transfected OVA lacks a signal peptide.…”

“…Indeed, B16F10 tumours can be eradicated by cytotoxic CD8 T-cells in vivo. [15][16][17] The application of next-generation sequencing and bioinformatics has shown that neoantigens produced by mutations in individual tumours are targets of antitumour immunity. The subcellular 0·7 0·9% 17% % Figure 5.…”

“…13,15,16 In contrast to immune-checkpoint blockade, cancer vaccines comprising tumour-associated or -specific antigens (Ags) prime and/or activate antitumour immune cells, such as cytotoxic T-cells. 17 Ag presentation under non-inflammatory conditions fails to elicit an adaptive immune response and can induce tolerance to the Ag. 17 Ag presentation under non-inflammatory conditions fails to elicit an adaptive immune response and can induce tolerance to the Ag.…”

Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools

“…Traditional cancer vaccines based on Tumor Associated Antigens (TAAs) have for the most part failed in clinical trials (80)(81)(82). Evidence that is now emerging suggests that the reason they have failed is because TAAs are broadly recognized as "Self " by the immune system.…”