Long lasting p53-specific T cell memory responses in the absence of anti-p53 antibodies in patients with resected primary colorectal cancer

Immunization with a P53 synthetic long peptide vaccine induces P53‐specific immune responses in ovarian cancer patients, a phase II trial

“…In these studies, 3 large pools of peptides were used and the amino acid sequence covered by p1-p2 was present in the first pool of peptides. This first pool of peptides was only sporadically recognized, whereas the second pool of p53 peptides (covering p3-p10) was predominantly recognized, 15,16 suggesting that peptides 1 and 2 of the p53-SLP do not encode HLA class II epitopes for the particular types of MHC class II molecules within this group of Dutch patients. Notably, scrutiny of vaccine-induced immunity vs. HLA class II (Table II) did not reveal any correlation between responsiveness and a particular HLA class II type indicating that the responses are likely to be restricted by multiple MHC class II molecules.…”

“…26 In view of the fact that p53 is over expressed in many types of tumors, p53-specific CD4 1 T cells may act as ''universal'' T-helper cells for cancer and act analogous to the observed clinical remission and immunological responses to antigens other than NY-ESO-1 after the infusion of NY-ESO-1-specific T-helper cells in a patient with metastatic melanoma. 27 Our analyses of the p53-specific CD4 1 Th-cell repertoire in patients with cancer showed that in general these responses were weak 15,16 and failed to produce any of the Th1 or Th2 key cytokines 17 or were polarized towards a noneffective Th2 response, 15 suggesting that the induction of a strong p53-specific Th1-response through immunization may enhance the efficacy of the anti-tumor response.…”

“…[10][11][12][13][14] Indeed, circulating and tumor-infiltrating p53-specific memory T-cells could be detected and isolated from patients with ovarian cancer but not benign ovarian tumors. 15 In addition, p53-specific memory T cells have been observed in patients with colorectal cancer [15][16][17] and breast cancer, 18 indicating that tumor-derived p53 can effectively be presented to the immune system and activate circulating p53-specific T-lymphocytes. Although accumulating evidence suggests that the p53-specific CD8 1 T-cell repertoire is restricted by self tolerance, 19,20 the CD4 1 T-cell repertoire is not affected.…”

“…In our current study, we used overlapping synthetic long peptides (SLP), constituting the most immunogenic part of the p53 protein, [15][16][17] to enhance the p53-specific immune response in patients with cancer. Because of their length, SLP are predominantly taken up by professional antigen presenting cells (APC) where they are processed for presentation by both MHC class I and II molecules.…”

Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients

“…4 Although p53 is an auto-antigen, it has been demonstrated that humoral and cellular immune responses against p53 can be detected in cancer patients. [5][6][7][8][9][10] Enhancing these responses could result in effective antitumor responses, but also induce a hazardous reaction to normal cells that have low expression levels of this auto-antigen.…”