Identification of an HLA‐DR‐restricted peptide epitope with a promiscuous binding pattern derived from the cancer testis antigen HOM‐MEL‐40/SSX2

Tapping CD4 T Cells for Cancer Immunotherapy: The Choice of Personalized Genomics

“…In some instances, peptides from unmutated tumor Ags bind different MHC class II alleles, so-called "promiscuous" peptides (79,(111)(112)(113)(114)(115). These peptides are therapeutically useful because they could be used to immunize a large segment of the human population.…”

Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells

“…Rather, for the present study and in light of the well-known promiscuous binding pattern of MHC class 2 peptides, it was advisable to include patients with unknown HLA status for the primary identification of CD4 ϩ T-cellstimulating epitopes. Although the HLA-DRB1*1401 restriction of the CD4 ϩ -mediated response to p635-649 has been established without any doubt by our experiments, a more promiscuous binding of this peptide to additional HLA-DR subtypes, as has been demonstrated for many other HLA-DR-restricted antigenic peptides, 16,19,[41][42][43] can be demonstrated or excluded only by analysis of a larger series of patients.…”

“…After NY-ESO-1 [14][15][16][40][41][42][43][45][46][47] and SSX-2, [17][18][19][20]48 HOM-TES-14/SCP1 is only the third of 16 cancer testis genes 13 originally detected by SEREX because of their ability to induce antibody response in the autologous host 10 for which coexisting T-cell reactivity has been demonstrated by reverse T-cell immunology.…”

“…26 A mix of 7 pentadecamers derived from pp65 of the human cytomegalovirus (CMV) and predicted to bind to the HLA-DR subtypes of interest (p32, p117, p243, p269, p299, p510, and p524) was used as positive control. 19 Peptides were synthesized according to the Fmoc/tBu strategy, as described. 27 Purity was greater than 90%, as assessed by high-performance liquid chromatography (HPLC) and mass spectrometry.…”

“…Even though the SEREX approach has considerably enlarged the pool of molecularly defined cancer testis antigens, 13 the ability of SEREX-defined antigen to induce T-cell responses has been demonstrated for only a few of them, namely NY-ESO-1 [14][15][16] and SSX2, [17][18][19][20] but not for SCP1, which has been shown to be the most frequently expressed CTA in a variety of neoplasms of different origin. [21][22][23][24] This holds particularly true for malignant lymphomas, in which other CTAs are rarely expressed.…”