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Publications (40)
PurposeAE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year o...
Background:
E39, an HLA-A2-restricted, immunogenic peptide derived from the folate-binding protein (FBP), is overexpressed in multiple malignancies. We conducted a phase I/IIa trial of the E39 + GM-CSF vaccine with booster inoculations of either E39 or E39' (an attenuated version of E39) to prevent recurrences in disease-free endometrial and ovari...
INTRODUCTION:
Patients(pts) with stage III-IV melanoma have a high risk of recurrence after resection despite standard of care therapies (SOC). Melanoma has proven to be immunogenic, and many novel treatment strategies targeting this have been initiated. We are conducting a phase IIb double-blind randomized trial of a vaccine consisting of autologo...
Introduction:
Tumor vaccines use various strategies to generate immune responses, commonly targeting generic tumor-associated antigens. The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from DC loaded with autologous tumor antigens, creating a patient-specific vaccine. Here, we describe initial phase I/IIa trial result...
Aim:
We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP).
Materials and methods:
Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotome...
In this randomized phase Ib trial, we tested combining the E39 peptide vaccine with a vaccine created from E39’, an attenuated version of E39.
Patients with breast or ovarian cancer, who were disease-free after standard of care therapy, were enrolled and randomized to one of three arms. Arm EE received six E39 inoculations; arm EE’ received three E...
75
Background: The treatment options for cancer are ever-evolving & now include vaccines targeting tumor-specific immunogenic peptides to induce tumor cytolysis. Folate binding protein (FBP) is a tumor-associated antigen (TAA) highly expressed in most endometrial & ovarian cancers (Ca), shielded from the normal immune system. The most promising FBP...
TPS201
Background: Melanoma is a potentially lethal skin malignancy; patients with stage III/IV resected disease have a recurrence rate of 50-90%. Adjuvant checkpoint inhibitor immunotherapy decreases the risk of recurrence but also causes significant immune-related toxicity. Vaccines are a promising strategy for patients with high risk melanoma. T...
INTRODUCTION: Peptide vaccines offer anti-tumor efficacy with very low toxicity. However, repeat stimulation with an immunogenic peptide leads to activation induced cell death (AICD), decreasing efficacy. We engineered variants of an immunogenic peptide (E39) and tested their ability to induce a robust, sustainable immune response.
METHODS: Multipl...
169
Background: Our current tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine employs yeast cell wall particles (YCWP) to deliver antigen to DC ex vivo and is being tested in a randomized phase IIb trial. This strategy may be improved by injecting TL-loaded YCWP as an intradermal vaccine, with in vivo DC uptake. Silicate capping should...
BACKGROUND FBP is overexpressed in 20-50% of breast(B) cancers(Ca) and roughly 90% of endometrial(E) and ovarian (Ov) Ca. E39 (FBP191-199, EIWTHSYKV)+GM-CSF is an HLA-A2 restricted FBP peptide vaccine, which has been shown to generate significant immunologic response(IR) in a phase I/IIa trial in E Ca and Ov Ca patients (pts). There is a risk of in...
Introduction: One of the most encouraging examples of targeted therapy for cancer is trastuzumab, but its success is dependent on levels of expression of its target, HER2. We have found that HER2 expression levels also have a significant impact on the efficacy of HER2-directed peptide vaccines. Analogous to HER2 in breast cancer, Folate Binding Pro...
Background: We have completed treatment in a phase I/IIa trial utilizing E39 (GALE-301, FBP 191-199, EIWTHSYKV), an HLA-A2 restricted, FBP-derived peptide + GM-CSF vaccine to prevent recurrence in EC and OC patients (pts). This vaccine has been shown to be safe and immunogenic, with promising early clinical results. Booster inoculations have improv...
Background:
Stage IV melanoma has high mortality, largely unaffected by traditional therapies. Immunotherapy including cytokine therapies and checkpoint inhibitors improves outcomes, but has significant toxicities. In this phase I/IIa trial, we investigated safety and efficacy of a dendritoma vaccine, an active, specific immunotherapy, in stage IV...
Introduction: We are conducting a phase II clinical trial of the GP2+GM-CSF vaccine for the prevention of breast cancer recurrence in disease-free, node-positive or high-risk node negative patients (pts). GP2 is an HLA-A2+-restricted immunogenic peptide from the HER2 protein (aa: 654-662) capable of stimulating CD8+ cytotoxic T-lymphocytes (CTLs) t...
Introduction: The majority of tumor vaccines (vax) target tumor-specific/associated antigens with a variety of delivery systems/immunoadjuvants. As opposed to testing an “off the shelf” vax to treat a subset of patients (pts), our approach is tailored to the specific pt but applicable to all pts, all tumors. Our vax uses autologous dendritic cells...
Background: We are conducting a phase II clinical trial of the HER2 peptide vaccine AE37+GM-CSF for prevention of breast cancer recurrence in disease-free, node-positive or high-risk node-negative patients (pts), who have completed standard of care therapy. AE37, an Ii-Key hybrid of the HER2-derived peptide AE36 (aa:776-790), is an MHC Class II epi...
Background:
Folate binding protein(FBP) is an immunogenic protein over-expressed in endometrial(EC) and ovarian cancer(OC). We are conducting a phase I/IIa trial of E39 (GALE 301)+GM-CSF, an HLA-A2-restricted, FBP-derived peptide vaccine to prevent recurrences in disease-free EC and OC patients. This interim analysis summarizes toxicity, immunolog...
Background: In an adjuvant phase II trial, the HER2-derived nelipepimut-S (E75) + GM-CSF vaccine (Neuvax) has been shown to reduce breast cancer recurrence. Preclinical testing of the combination of trastuzumab (Tz) and nelipepimut-S has shown synergistic cytolysis against HER2 expressing cancer cells. In pilot phase II data in HER2+ patients (pts)...
134 Background: GP2 is a HER2 derived, HLA-A2+-restricted immunogenic peptide designed to stimulate CD8+T cells to recognize tumor cells with any level of HER2 expression (IHC 1-3+). Accrual to a prospective, randomized, multi-center, phase II trial of the GP2 vaccine for prevention of breast cancer recurrence has completed. Here, the planned prima...
The management of vascular trauma in pediatric patients presents numerous challenges, especially in an austere environment. We present the case of a 3-year-old girl who sustained multiple fragmentation injuries to the right chest and right upper extremity as a result of combat activity in Iraq. This resulted in an occult pseudoaneurysm of the innom...
