MHC Class I–Presented Tumor Antigens Identified in Ovarian Cancer by Immunoproteomic Analysis Are Targets for T-Cell Responses against Breast and Ovarian Cancer

Abstract

Purpose: The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans.Experimental Design: Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancerassociated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials.Results: T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells.Conclusion: Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients.

First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients

“…We have previously described and tested this vaccine candidate in preclinical models [5,11]. The vaccine-incorporated peptides are presented by MHC class I on the cell surface of breast, ovarian and prostate cancer cells, but not on normal cells [6]. Their inclusion in DPX-0907 yields an immunogenic vaccine in HLA-A2 transgenic mice that promotes the activation of both Type 1 T cell responses, while minimizing the induction of regulatory mechanisms [11].…”

Dengue virus specific dual HLA binding T cell epitopes induce CD8+T cell responses in seropositive individuals

“…Importantly, a multi-peptide vaccine formulation is a feasible approach, as multiple peptides capable of inducing robust CD8 C T cell responses can be included in the vaccine without significant competition for binding to HLA molecules. [45][46][47] The immunoproteomics approach capable of identifying T cell epitopes specific for any HLA supertype or multiple HLA supertypes further extends the prospect for universal prophylactic and therapeutic T cell vaccine for many infectious diseases including dengue virus infection.…”

Quantitative immunoproteomics analysis reveals novel MHC class I presented peptides in cisplatin-resistant ovarian cancer cells

“…A number of such tumor-specific peptides have already been identified and some have been successfully tested as cancer vaccines in humans, most notably for immunotherapy of melanoma [39] and other cancers including ovarian cancer [40]. In the present study, employing a quantitative immunoproteomics method, we identified 952 MHC peptides in cisplatin-sensitive and resistant ovarian cancer cells (SKOV3-A2, SKOV3-A2-CP and OVCAR3) with a large number of them up-regulated in the cisplatin-resistant ovarian cancer cells.…”