Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments

Abstract

Personalized neoantigen vaccines are a highly specific cancer treatment designed to induce a robust cytotoxic T-cell attack against a patient’s cancer antigens. In this study, we searched ClinicalTrials.gov for neoantigen vaccine clinical trials and systematically analyzed them, a total of 147 trials. Peptide vaccines are the largest neoantigen vaccine type, comprising up to 41% of the clinical trials. However, mRNA vaccines are a growing neoantigen vaccine group, especially in the most recent clinical trials. The most common cancer types in the clinical trials are glioma, lung cancer, and malignant melanoma, being seen in more than half of the clinical trials. Small-cell lung cancer and non-small-cell lung cancer are the largest individual cancer types. According to the results from the clinical trials, neoantigen vaccines work best when combined with other cancer treatments, and popular combination treatments include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Additionally, half of the clinical trials combined neoantigen vaccines with an adjuvant to boost the immune effects, with poly-ICLC being the most recurrent adjuvant choice. This study clarifies the rapid clinical trial development of personalized neoantigen vaccines as an emerging class of cancer treatment with increasingly diversified opportunities in classes, indications, and combinatorial treatments.

HLA class I peptidome analysis of synthetic long peptide-fed human dendritic cells for therapeutic vaccine design

“…A commonly used TLR3-ligating adjuvant in the clinic is the double stranded RNA analogue Hiltonol™, which is a derivative of polyriboinosinic-polyribocytidylic acid (Poly(IC:)) 23 . Last reported in 2022, it has been the adjuvant of choice for neoantigen vaccines 24 . In addition, adjuvants targeting the heterodimer TLR1/2 have demonstrated good potential alongside SLP vaccines [25][26][27] .…”

Targeted Acidosis Mediated Delivery of Antigenic MHC-Binding Peptides

“…42 Additionally, recent clinical trials have demonstrated the effectiveness of delivering cancer-specific neoantigens for display on MHC in use for cancer therapy. 43…”

“…42 Additionally, recent clinical trials have demonstrated the effectiveness of delivering cancer-specific neoantigens for display on MHC in use for cancer therapy. 43 Building upon these findings, we posed that pHLIP could deliver antigenic peptides to cancer cells and this would offer a novel approach to selectively activate the immune system against cancer cells. Here, we showed that pHLIP conjugated to the model antigen SIINFEKL is selectively translocated through the membrane of cells in low pH environments and is subsequently displayed on MHC (Figure 1).…”

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

“…Recently, they are further boosted by developing biomedicine-based nanotechnologies, such as mRNA vaccines consisting of lipid nanoparticles . Currently, many cancer vaccines have been registered and used in clinical trials. , Cancer vaccines are expected to lead a round of immunotherapeutic revolutions such as immune checkpoint blockers (ICBs). Nevertheless, some barriers restrict the expansion of cancer vaccines in clinics .…”

“…1 Currently, many cancer vaccines have been registered and used in clinical trials. 2,3 Cancer vaccines are expected to lead a round of immunotherapeutic revolutions such as immune checkpoint blockers (ICBs). Nevertheless, some barriers restrict the expansion of cancer vaccines in clinics.…”