Table 4.
Vaccines targeting HER2+ breast cancer
| Name of vaccine (institution/company) | Description | Clinical trial ID | Trial design/patient population | Published clinical trial data | Reference |
|---|---|---|---|---|---|
| Peptide/protein-based vaccines | |||||
| Nelipepimut-S/ NeuVa (Galena Biopharma) | MHC class I vaccine derived from the HER2 ECD | NCT01479244 | PRESENT phase III: NeuVax vs GM-CSF in node+ BC with low to intermediate HER2 expression | No difference in DFS in patients treated with Neuvax + GM-CSF vs GM-CSF alone | Mittendorf et al.203 |
| AE37 (NuGenerex Immuno-Oncology; Norwell, Inc.) | MHC class II peptide derived from the intracellular domain of HER2 | NCT00524277 | Phase II: AE37 + GM-CSF vs GM-CSF in BC with any HER2 expression | No differences in recurrences rates or DFS between the two arms | Mittendorf et al.202 |
| GP2 (NuGenerex Immuno-Oncology; Norwell, Inc.) | HER2-derived HLA-A2- and HLA-A3-restricted epitope | NCT00524277 | Phase II: GP2 + GM-CSF vs GM-CSF in high-risk BC with any level of HER2 | No difference in DFS between the two arms | Mittendorf et al.233 |
| GLSI-100 (Greenwich LifeSciences, Inc.) | HER2-derived HLA-A2- and HLA-A3-restricted epitope (GP2 + GM-CSF) | NCT05232916 | Phase III: HER2/neu peptide GLSI-100 vs placebo in HER2+ BC | Not applicable | NCT05232916 |
| TPIV100 (NCI) | HER2 multiple epitope-based vaccine | NCT04197687 | Phase II randomized: T-DM1 + GM-CSF + TPIV100 or placebo in HER2+ BC with residual disease after NAC | Not applicable | NCT04197687 |
| MVF-HER-2 (597-626)-MVF-HER-2 (266-296) (Ohio State University Comprehensive Cancer Center) | Two chimeric peptides cosynthesized with B cell epitopes derived from HER2 ECDs 2 and 4 | NCT01376505 | Phase I: advanced solid tumours including HER2+ MBC | 2 PRs (6%); vaccine-generated sustained humoral response | Bekaii-Saab et al.234 |
| dHER2 (GlaxoSmithKline) | Recombinant protein comprising the ECD and a fragment of the ICD combined with the adjuvant AS15 | NCT00952692 | Phase I/II: dHER2 + lapatinib in trastuzumab-refractory HER2+ MBC | Anti-HER2 antibodies detected in all patients; OS at 300 days was 92% | Hamilton et al.194 |
| Whole cell-based vaccines | |||||
| HER2+, GM-CSF secreting vaccine (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins) | Allogeneic, HER2+ GM-CSF-secreting breast tumour vaccine | NCT00399529 | Phase II: MBC (including HER2+ MBC) treated with vaccine + chemotherapy | HER2-specific T helper-dependent immunity and antibody responses detected to vaccine | Emens et al.235 |
| HER2+, GM-CSF secreting vaccine (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins) | Allogeneic, HER2+ GM-CSF-secreting breast tumour vaccine | NCT00093834 | Phase I: cyclophosphamide + vaccine + weekly trastuzumab for HER2+ MBC | PFS 7 mo; OS 42 mo; HER2-specific immunity was detected | Chen et al.195 |
| Dendritic cell-based vaccines | |||||
| HER2-dendritic cell vaccine (Duke University) | DCs loaded with HER2 ICD | NCT00005956 | Pilot: HER2 ICD DC vaccine vs DC vaccine containing tetanus/CMV control for patients with stage II–IV HER2+ BC post surgery | >5-year follow-up 6/7 patients had circulating anti-HER2 ICD antibodies and all alive and disease free | Morse et al.196 |
| DC1 vaccine (Abramson Cancer Center of the University of Pennsylvania) | HER2 ECD and ICD peptide-pulsed DC vaccine | NCT02061332 | Phase I/II: HER2+ DCIS or IBC vaccinated intratumourally, in nodes or both | pCR higher in DCIS vs invasive BC (28.6% vs 8.6%); immune responses detected in nodes were associated with pCR | Lowenfeld et al.198 |
| DNA-based vaccines | |||||
| pNGVL3-hICD (University of Washington) | HER2 ICD DNA plasmid-based vaccine | NCT00436254 | Phase I: stage III/IV HER2+ BC in remission or stable bone-only disease treated with intradermal plasmid-based vaccine | Intermediate dose (100 μg) was immunogenic and associated with persistence of immunity at 60 weeks; PFS and OS not reached | Disis et al.236 |
| WOKVAC (University of Washington) | Plasmid-based DNA with three epitopes: IGFBP2, HER2 and IGF1R | NCT04329065 | Phase II: vaccine + paclitaxel + trastuzumab + pertuzumab as neoadjuvant therapy for HER2+ BC | Not applicable | NCT04329065 |
| WOKVAC (H. Lee Moffitt Cancer Center and Research Institute) | Plasmid-based DNA with 3 epitopes: IGFBP2, HER2 and IGF1R | NCT03384914 | Phase II: WOKVAC vs DC1 vaccine in HER2+ stage I–III BC with residual disease post NAC | Not applicable | NCT03384914 |
| Virus-based vaccines | |||||
| VRP-HER2 (Duke University) | Alphaviral vector encoding the ECD and transmembrane domains of HER2 (VRP-HER2) | NCT01526473 | Phase I: VRP-HER2 monotherapy or combination with anti-HER2 therapy in HER2+ MBC | One PR and two SDs reported; HER2-specific CD8+ T cells detected; median OS 50.2 mo with vaccine only and 32.7 mo with combination | Crosby et al.201 |
| VRP-HER2 (Duke University) | Alphaviral vector encoding the ECD and transmembrane domains of HER2 (VRP-HER2) | NCT03632941 | Phase II: VRP-HER2 ± pembrolizumab vs pembrolizumab alone in HER2+ MBC | Not applicable | NCT03632941 |
BC, breast cancer; CMV, cytomegalovirus; DC, dendritic cell; DCIS, ductal carcinoma in situ; DFS, disease-free survival; ECD, extracellular domain; GM-CSF, granulocyte–macrophage colony-stimulating factor; IBC, inflammatory breast cancer; ICD, intracellular domain; IGF1R, insulin-like growth factor 1 receptor; IGFBP2, insulin-like growth factor-binding protein 2; MBC, metastatic breast cancer; MHC, major histocompatibility complex; mo, months; NAC, neoadjuvant chemotherapy; ORR, objective response rate; OS, overall survival; pCR, pathological complete response; PFS, progression-free survival; PR, partial response; SD, stable disease; T-DM1, ado-trastuzumab emtansine.