A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma: preliminary report

Identification of a naturally processed HLA‐A*0201 HPV18 E7 T cell epitope by tumor cell mediated in vitro vaccination

“…11,[15][16][17][18] Recent studies strongly implicate that CD8ϩ T cell-mediated, cytolytic responses play an essential role in regression of precancerous lesions and tumors, with CD4ϩ T cells being important for the development of an efficient immune response. 5,12,[15][16][17][18][19][20] For the development of peptide-based vaccines and for monitoring of the induction of specific T cells via vaccination, the knowledge of cytolytic T cell epitopes of the E6 and E7 antigens is necessary. Several epitopes have been identified for the most prevalent HPV type 16.…”

“…Screening by the use of a long synthetic 20mer peptide library allowed us to identify an epitope that would not have been predicted with high priority by the computer program. The lack of response to the 20mer HPV18 E7 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] that includes the high affinity binding peptide HPV18 E7 7-15 described by Rudolf et al 24 would have excluded this potential epitope from further analysis as an irrelevant epitope. Consequently, we never found a response to this epitope.…”

“…In this library, consequently, all possible epitope sequences of the HPV18 E7 were represented. Sequences are: HPV18 E7 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , p44 (MHGP-KATLQDIVLHLEPQNE); HPV18 E7 [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] , p45 (VLHLEPQNE-IPVDLLCHEQL); HPV18 E7 , p46 (VDLLCHEQLSDSEEEN-DEID); HPV18 E7 34 -53 , p47 (SEEENDEIDGVNHQHLPARR); HPV18 E7 [45][46][47][48][49][50][51][52][53]…”

“…12,19,20 To investigate HPV18 E7 86 -94 -specific cytolysis by T cells without a background of allo-reactivity we generated peptide-specific T-cell lines. PBL from HLA-A2-positive healthy blood donors (Donor 6 and Donor 7) were stimulated with autologous PBL loaded with HPV18 E7 86 -94 peptide (20 g/ml).…”

“…CD8ϩ T cell mediated, cytolytic responses were identified to play an essential role in regression processes, though CD4ϩ T cells may also be induced and important for an efficient immune response. 5,12,[15][16][17][18][19][20] For the development of vaccines and the monitoring of the immune response of the treated patients, knowledge of relevant CTL epitopes of E6 and E7 is indispensable.…”