Assessing the role of a mutant ras peptide-based vaccine as adjuvant immunotherapy in patients with solid tumors: We developed a Quantitative real-time PCR assay as novel method to test class II responses on this protocol to check the patients samples. We found on this trial that it is feasible to vaccinate patients with pancreatic and colon cancer on an adjuvant basis. We demonstrated in this phase II study the generation of specific immunological responses and an indication of better DFS and OS of this population than after standard therapy. (Manuscript in review)) Vaccine against the P53 antigen: In collaboration with Gynecologic Oncology Group and Dr. Theresa Whiteside at University of Pittsburgh, we have completed a clinical trial to test vaccinating patients with low burden ovarian cancer with a wild type HLA-A2 p53 epitope. We found for the first time that the majority of patients with tumor that overexpress p53 can generate specific immune responses against the antigen. In this trial we are also comparing 2 strategies for peptide delivery methods: subcutaneous vs. intravenous Vaccine against Human Papillomavirus (HPV):In collaboration with the Gynecologic Oncology Group, we have just completed a clinical trial in advanced cervical cancer patients. These patients were vaccinated with either E6 or E7 peptides. We found that it is feasible to vaccinate this group of heavily pretreated patients with peptides and they can efficiently generate immune responses against the Human papillomavirus antigens. The immunological testing on the rest of the patients is expected to be completed very soon. (2 manuscripts will be submitted for publication in October).Vaccine against angiogenesis:Based on our preclinical data that we generated in the lab, we are developing a protocol to vaccinate advanced renal cancer patients with HLA-A2 VEGFR2 peptides. This will be the first study in human targeting angiogenesis in a vaccine strategy. protocol has been approved by PRMC and IRButilize reagents to inhibit the suppressive effect of the immune system. this includes CT011 anti PD1 antibody and Amp224.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Mkrtichyan, Mikayel; Najjar, Yana G; Raulfs, Estella C et al. (2012) B7-DC-Ig enhances vaccine effect by a novel mechanism dependent on PD-1 expression level on T cell subsets. J Immunol 189:2338-47
Rahma, Osama E; Ashtar, Ed; Czystowska, Malgorzata et al. (2012) A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients. Cancer Immunol Immunother 61:373-84
Rahma, Osama E; Khleif, Samir N (2011) Therapeutic vaccines for gastrointestinal cancers. Gastroenterol Hepatol (N Y) 7:517-64
Mkrtichyan, Mikayel; Najjar, Yana G; Raulfs, Estella C et al. (2011) Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms. Eur J Immunol 41:2977-86
Meyskens Jr, Frank L; Curt, Gregory A; Brenner, Dean E et al. (2011) Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic. Cancer Prev Res (Phila) 4:311-23
Rahma, Osama E; Ashtar, Ed; Ibrahim, Ramy et al. (2010) A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic renal cell carcinoma. J Transl Med 8:8