Table 1. HLA-restricted epitope vaccines against cancer.
Protein | Epitope | Adjuvant | Patients/Animals | Methods | Results | Ref. |
---|---|---|---|---|---|---|
MUC1 | CT3–27(CQCRRKNYGQ LDIFPARDTY HPMSEYPTYH)(#1) CT18–49(HPMSEYPTYH THGRYVPPSS TDRSPYEKVS AG)(#2) CT37–69(STDRSPYEKV SAGNGGSSLS YTNPAVAAAS ANL)(#3) MUC1 TR (PDTRPAPGST APPAHGVTSA) |
GM-CSF | transgenic mice for human MUC1 (MUC1.Tg) |
The mice was injected with a combination of 50μg of peptide#1, 50μg of peptide #2, and 50μg of peptide #3 in a total volume of 100μl. | survival can be significantly prolonged in vaccinated MUC1.Tg mice challenged with MUC1-expressing tumor cells, without induction of autoimmune responses | 37 |
CEA | CEA625–667 | aluminum hydroxide gel | Female BALB/c mice | Mice were immunized intramuscularly with 100μg of pcDNA3.0, pcDNA-CEA625–667, or pcDNA-triCEA625–667 in 1:1 (v/v) of 3% aluminum hydroxide gel, respectively. | Induced strong antigen-specific T cell proliferation. Triple-repeated CEA peptides vaccine significantly elevated levels of IFN-γsecreted by T cells |
39 |
MAGE | MAGE-A3112–120 (KVAELVHFL) MAGE-A3271–279 (FLWGPRALV) |
HLA-A*0201 transgenic mice | Mice were immunized at the base of the tail with 100 mg of MAGE-A3112–120 (KVAELVHFL) or MAGE-A3 271–279 (FLWGPRALV) plus 120 mg of hepatitis B virus core |
generate high-avidity TCRs against MAGE-A3. | 43 | |
MAGE-1 peptide (EADPTGHSY) | HLA-A1 positive and melanoma cells expressed the MAGE-1 peptide, (EADPTGHSY) patients. |
Four monthly intradermal injections of increasing numbers of peptide-pulsed APCs (l05, 5 × l0,5 106, and 107cells) for the four consecutive injections. | Induced autologous melanoma-reactive and peptide-specific cellular CTL response. | 54 | ||
MAGE-A4278–299 (ALAETSYVKV LEHVVRVNAR VR) MAGE-A4143–154 (NYKRCFPVIF GK) |
OK432 Montanide ISA-51 |
pulmonary metastatic colon cancer patients. | The patient was vaccinated with 1 or 10 mg MAGE-A4-H/K-HELP mixed with OK432 (0.02KE) and Montanide ISA-51 four times at 2-week intervals | Induced MAGE-A4-specific Th1 and T-cell 1 immune responses and the production of MAGE-A4-specific complement-fixing IgG antibodies. Significantly decreased Tumor growth and carcinoembryonic antigen tumor marker. |
55 | |
gp100 | gp100 (IMDQVPFSV, 209–217(210 M)) |
Interleukin-2 Montanide ISA-51 |
Stage III, IV cutaneous melanoma, expression of HLA-A0201, an absence of brain metastases | Patients were treated with gp100 peptide plus Montanide ISA-51 once every 3 weeks, followed by interleukin-2 intravenous bolus every 8 h. | Compared with interleukin-2 alone, vaccine plus interleukin-2 significantly improved clinical response rate (16% vs. 6%) and progression-free survival (2.2 mo; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 mo; 95% CI, 1.5 to 1.8). | 53 |
HER-2/neu | AE37 (Ac-LRMKGVGSPY VSRLLGICL-NH2, Ii-Key hybrid of HER-2/neu peptide 776–790) |
GM-CSF | Disease-free, node-negative breast cancer patients. | Each person received 100 μg, 500 μg or 1000 μg of AE37 peptide mixed with 250 μg, 125 μg, 30 μg or 0 μg GM-CSF inoculations for 6 mo. | The optimal biologic dose (OBD) of the novel AE37 hybrid vaccine: 500 μg of peptide with GM-CSF (30–125 μg) which significantly increased in proliferative responses at long-term follow-up. | 57 |
HER-2/neu | E75 (KIFGSLAFL, HER-2/neu; 369–377) |
GM-CSF | Disease-free lymph node-positive (NP), lymph node-negative (NN) and HLA-A2/A3 breast cancer patients, | Patients were vaccinated over 6 mo (3, 4, or 6 times) with different doses of E75 (100 μg, 500 μg, or 1000 μg) plus GM-CSF (250 μg or 125 μg). |
Phase I The optimal biologic dose (OBD): 1000 μg E75 plus 250 μg GM-CSF monthly × 6. Phase II 24 mo landmark analysis disease free survival (DFS): Vaccinated group, 94.3%; control group, 86.8%. |
59 |
HER-2/neu | GP2 (IISAVVGIL HER-2/neu, 654–662) |
GM-CSF | Disease-free, lymph node-negative and HLA-A2 breast cancer patients | Patients received 100 μg, 500 μg, or 1000 μg of GP2 peptide mixed with 250 μg of GM-CSF. | Elicit an significant immune response . | 61 |