Table 1.
Helper peptide vaccines with favorable immunologic and/or clinical outcomes
| Cancer target | Source proteins: Peptides in vaccines |
Adjuvant/delivery | Immunologic outcome |
Clinical outcomes |
|---|---|---|---|---|
| Invasive breast cancer, DCIS | [Her2/neu]: Her2 (42-56), (98-114), (328-345), (776-790), (927-941), (1166-1180) +/− HLA-A2 peptides Her2 (369-377), (689-697) | Peptide-pulsed type 1 DC (matured in IFNγ and LPS), intranodal. Also evaluated intralesional vaccines. | Durable TCD4 responses in about 80% of patients [48]. | Complete regressions of DCIS in 19%–29%; decreased Her2 expression [49] [50]. |
| NSCLC and pancreatic cancer | [hTERT]: GV1001 vaccine: hTERT (611-626) | Administered to patients with NSCLC and also with gemcitabine for patients with pancreatic cancer. | Polyfunctional Th1 cells induced to hTERT (59%); epitope spreading to Ras (29%), but transient and weak responses.[51] | Survival for NSCLC enhanced in immune responders (54 vs. 13 mos, p<0.001) [52]. Failed to impact survival in randomized phase III trial [55]. |
| Prostate cancer, renal cell cancer | [hTERT]: GX301 vaccine: hTERT (611-626), (672-686), (766-780); plus HLA-A2 restricted hTERT (540-548) | Each peptide administered with IFA and topical imiquimod in the skin of the abdomen: each peptide in a different site. Each vaccine administration in the same sites. | Immune response in all patients. | SD in 4 patients |
| Melanoma | [gp100, tyrosinase]: HLA-A2 restricted: gp100 (154–162); tyros (369– 377); +/− MHC-II– restricted gp100 (44–59); tyros (448–462). | Monocyte-derived DC prepared in IL4, GM-CSF and matured PGE2 and TNFa. Also pulsed with KLH. Intranodal injection. | IFNγ response of SKIL to melanoma cells 29% vs 7%; Tetramer+ in blood 17% vs 0% for TCD8, 23% for TCD4. | PFS enhanced for addition of helper peptides (5 vs 2.8 mos, p < 0.01) |
| Melanoma | [gp100, tyrosinase, MelanA, MAGE-A] 6MHP vaccine: gp100 (44-59); tyros (56-70); tyros (386-406); Melan-A (51-73); MAGE-A3 (281-295); MAGE-A1-3,6 (121-134); | Peptides + IFA +/− GM-CSF, administered half SC, half ID. | TCD4 response in 81% (blood or node); epitope spreading to TCD8 responses (different antigens) in 45% tested; induction of Ab responses. | ORR 7–12% (duration up to 7 years). Survival associated with TCD4 response. Survival exceeds matched controls. 5 year survival 74% for resected stage IV. |
Abbreviations: AdenoCA = adenocarcinoma; tyros = tyrosinase; SKIL = skin test infiltrating lymphocytes; LPS = lipopolysaccharide; IN = intranodal; SC = subcutaneous; ID = intradermally; ORR = objective response rate (PR + CR); NSCLC: non small cell lung cancer.
Amino acid sequences of selected peptides are: gp100154–162(KTWGQYWQV); gp100280–288(YLEPGPVTA); tyros369–377(YMDGTMSQV); gp10044–59(WNRQLYPEWTEAQRLD); tyros448–462(DYSYLQDSDPDSFQD); tyros56-70(AQNILLSNAPLGPQFP); tyros386-406(FLLHHAFVDSIFEQWLQRHRP); Melan-A51-73(RNGYRALMDKSLHVGTQCALTRR); MAGE-3281-295(TSYVKVLHHMVKISG); MAGE-1,2,3,6121-134(LLKYRAREPVTKAE); hTERT611-626(EARPALLTSRLRFIPK)