Feasibility of Personalized Peptide Vaccination for mrTNBC
Introduction Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.
Methods Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.
Results No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.
Conclusions PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.
Recent advances in chemotherapies, hormonal therapies and anti-human epidermal growth factor receptor 2 (HER2) therapies have significantly improved the prognosis in metastatic recurrent breast cancer patients. For example, new chemotherapies using agents such as nanoparticle albumin-bound paclitaxel (nab-PTX), eribulin mesylate and bevacizumab, new hormonal therapies such as fluvestrant injection or new anti-HER2 therapies such as those using pertuzumab and trastuzumab emtansine (T-DM1) have shown significant clinical benefits in metastatic recurrent breast cancer patients. Despite these novel therapeutic advances, the treatment modalities for chemotherapy-resistant triple-negative breast cancer (TNBC) remain limited, and thus a novel treatment approach including immunotherapy is required. Nevertheless, no randomized controlled trials of cancer vaccine have shown promise of clinical benefit for metastatic recurrent breast cancer patients, particularly in metastatic recurrent TNBC (mrTNBC).
We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are selected from a pool of 31 different peptide candidates based on the pre-existing immunoglobulin G (IgG) responses specific to each peptide before vaccination. Most of the peptides employed for PPV, except for those derived from prostate-related antigens, are known to be commonly expressed in various types of advanced cancers. Our previous clinical trials of PPV for patients with advanced cancers demonstrated the safety and feasibility of this new approach. Here we conducted a phase II study of PPV for metastatic recurrent breast cancer to investigate the feasibility of PPV for mrTNBC.
Abstract and Introduction
Abstract
Introduction Since treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.
Methods Seventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.
Results No severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.
Conclusions PPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.
Introduction
Recent advances in chemotherapies, hormonal therapies and anti-human epidermal growth factor receptor 2 (HER2) therapies have significantly improved the prognosis in metastatic recurrent breast cancer patients. For example, new chemotherapies using agents such as nanoparticle albumin-bound paclitaxel (nab-PTX), eribulin mesylate and bevacizumab, new hormonal therapies such as fluvestrant injection or new anti-HER2 therapies such as those using pertuzumab and trastuzumab emtansine (T-DM1) have shown significant clinical benefits in metastatic recurrent breast cancer patients. Despite these novel therapeutic advances, the treatment modalities for chemotherapy-resistant triple-negative breast cancer (TNBC) remain limited, and thus a novel treatment approach including immunotherapy is required. Nevertheless, no randomized controlled trials of cancer vaccine have shown promise of clinical benefit for metastatic recurrent breast cancer patients, particularly in metastatic recurrent TNBC (mrTNBC).
We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are selected from a pool of 31 different peptide candidates based on the pre-existing immunoglobulin G (IgG) responses specific to each peptide before vaccination. Most of the peptides employed for PPV, except for those derived from prostate-related antigens, are known to be commonly expressed in various types of advanced cancers. Our previous clinical trials of PPV for patients with advanced cancers demonstrated the safety and feasibility of this new approach. Here we conducted a phase II study of PPV for metastatic recurrent breast cancer to investigate the feasibility of PPV for mrTNBC.