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Biomedical subjects

George E Peoples

Publications and source records attributed to George E Peoples.

At least 19 recordsLinked to original sources
PubMed2006

Investigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancer.

BACKGROUND: Trastuzumab, an anti-HER2/neu monoclonal antibody, is thought to promote HER2/neu receptor internalization and/or turnover. This study was designed to investigate the kinetics of trastuzumab treatment on tumor cells with varying levels of HER2/neu expression and to determine the effect of trastuzumab on HER2/neu-specific cytotoxic T lymphocyte-mediated lysis. METHODS: Three cell lines with varying levels of HER2/neu expression were incubated with varying doses of trastuzumab at multiple time points. Trastuzumab binding and HER2/neu expression were determined. Peripheral blood mononuclear cells from three HLA-A2(+) healthy donors and four E75 peptide-vaccinated patients were stimulated with HER2/neu-derived peptides and tested in standard chromium release cytotoxicity assays with HER2/neu(+) tumor cells pretreated with trastuzumab. RESULTS: Treatment of tumor cells with 10 microg/mL of trastuzumab in an overnight incubation resulted in saturation of cell-surface HER2/neu receptors. At higher doses, trastuzumab staining and HER2/neu expression decreased in a time-dependent manner. Pretreatment of tumor cells with trastuzumab resulted in increases in specific cytotoxicity by peptide-stimulated cytotoxic T lymphocytes from HLA-A2(+) donors over untreated cells by an average of 5.6% and 15.3% (P = .0002) for doses of 10 and 50 microg/mL, respectively. In similar experiments involving peripheral blood mononuclear cells obtained from immunized patients, the average specific cytotoxicity for untreated cells was 34.2% +/- 1.3% vs. 40.6% +/- 2.5% (P = .035) and 40.7% +/- 1.6% (P = .0005) for those treated with 10 and 50 microg/mL, respectively. CONCLUSIONS: Our data suggest that pretreatment of breast cancer cells with trastuzumab induces turnover of the HER2/neu protein and enhanced killing by HER2/neu peptide-stimulated CTLs. This increased lysis occurs regardless of the degree of HER2/neu expression and seems more pronounced in vaccinated patients. These findings support further investigation into the use of combination immunotherapy with trastuzumab and HER2/neu peptide-based vaccines.

Antibodies, Monoclonal↗
PubMed2006

Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine.

We are conducting clinical trials of the E75 peptide as a vaccine in breast cancer (BrCa) patients. We assessed T cell subpopulations in BrCa patients before and after E75 vaccination and compared them to healthy controls. We obtained 17 samples of blood from ten healthy individuals and samples from 22 BrCa patients prior to vaccination. We also obtained pre- and post-vaccination samples of blood from seven BrCa patients who received the E75/GM-CSF vaccine. CD4, CD8, CD45RA, CD45RO, and CCR7 antibodies were used to analyze the CD4+ and CD8+ T cells by four-color flow cytometry. Compared to healthy individuals, BrCa patients have significantly more memory and less naïve T cells and more effector-memory CD8+ and less effector CD4+ T cells. Phenotypic differences in defined circulating CD4+ and CD8+ T cell subpopulations suggest remnants of an active immune response to tumor distinguished by a predominant memory T cell response and by untapped recruitment of naïve helper and cytotoxic T cells. E75 vaccination induced recruitment of both CD4+ and CD8+ naïve T cells while memory response remained stable. Additionally, vaccination induced global activation of all T cells, with specific enhancement of effector CD4+ T cells. E75 vaccination causes activation of both memory and naïve CD4+ and CD8+ T cells, while recruiting additional naïve CD4+ and CD8+ T cells to the overall immune response.

Antigens, CD↗
PubMed2006

Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine.

PURPOSE: We are conducting clinical trials in breast cancer (BrCa) patients to test the HER2/neu peptide vaccine (E75). We have investigated the impact of this vaccine on circulating levels of regulatory T cells (Treg) and the resulting effects on antitumor responses. EXPERIMENTAL DESIGN: Twenty-two blood samples from healthy individuals and from 22 BrCa patients including pre- and post-vaccination samples from seven vaccinated HLA-A2+ patients were stained for CD4, CD25, and CD69 as well as CD8 and E75:HLA-A2 Ig dimer and quantified by flow cytometry. Cytotoxic activity against HER2/neu+ tumors was measured by 51Cr-release. Serum from BrCa patients and normal subjects were analyzed for TGF-beta levels. RESULTS: BrCa patients have a greater percentage of circulating Treg (CD4+CD25+, 4.45% versus 2.96%; p=0.007) than normal subjects. HLA-A2+ BrCa patients had more Treg compared to the HLA-A2- BrCa patients (CD4+CD25+, 5.63% versus 3.28%; p=0.001). E75 vaccination increased circulating activated CD4+ T cells post-vaccination (CD4+CD69+, 1.23 versus 3.81%; p=0.03). However, T(reg) were significantly reduced after vaccination (CD4+CD25+, 5.31-1.81%; p<0.0001). Furthermore, activated Treg also decreased (CD4+CD25+CD69+, 0.23% versus 0.08%; p=0.06). Importantly, post-vaccination decreases in Treg were temporally associated with increased E75 vaccine-specific CD8+ T cells and corresponding HER2/neu+ tumor cytotoxicity. Serum TGF-beta levels were significantly elevated in BrCa patients compared to normals (3548 pg/ml versus 1007 pg/ml; p=0.007). Four of seven vaccinated patients showed decreased serum TGF-beta levels post-vaccination. CONCLUSIONS: Treg, are increased in BrCa patients along with serum levels of TGF-beta. E75 vaccination resulted in CD4+ recruitment but was associated with a significant decrease in circulating Treg and TGF-beta levels in the majority of the vaccinated patients. Successful cancer vaccination strategies may require the alteration of complex immune interactions.

Antigens, CD↗
PubMed2006

Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trial.

BACKGROUND: E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. The purpose of this study was to further investigate GP2 for potential use in vaccination strategies. Importantly, a naturally occurring polymorphism (I-->V at position 2, 2VGP2) associated with increased breast cancer risk was addressed. METHODS: Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with autologous dendritic cells (DC) pulsed with GP2 and tested in standard cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 targets. Additional cytotoxicity experiments used effectors stimulated with DC pulsed with E75, GP2, or the combination of E75+GP2. RESULTS: GP2-stimulated prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and the HLA-A2- control target SKOV3 of 28.8+/-3.7% (P<.01), 29.5+/-4.0% (P<.01), and 16.9+/-2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells lysed HER2/neu+ targets at 43.8+/-5.2% versus 44.2+/-5.7% for E75 (P=.87). When combined, an additive effect was noted with 58.6+/-5.4% lysis (P=.05). GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6+/-5.7%) and 2VGP2-loaded T2 targets (17.7+/-5.2%). CONCLUSIONS: GP2 is a clinically relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; therefore, a GP2 vaccine should be effective in patients carrying this polymorphism. GP2 may be most beneficial used in a multiepitope vaccine.

Breast Neoplasms↗
PubMed2006

Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients.

PURPOSE: We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast cancer patients in relationship to their clinicopathologic variables and immune response to a /neu E75 vaccine. EXPERIMENTAL DESIGN: We measured MCP-1 levels in 32 /neu(+) breast cancer patients before and after vaccination with a /neu E75 peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical prognostic variables were collected. Vaccine-specific immunologic responses were monitored. RESULTS: Serum MCP-1 levels >250 pg/mL (MCP-high) correlated with favorable prognostic variables. MCP-high patients compared with MCP-low (<250 pg/mL) patients showed statistically significant later onset of disease, earlier stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high patients had increased levels of preexisting immunity when compared with MCP-low patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher inducible levels of MCP-1 compared with MCP-high patients (median increase, 41% versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with >50% increase in MCP-1 levels (response-high) had worse clinical prognostic variables compared with patients with <50% increase (response-low). Response-high patients had statistically significant more poorly differentiated tumors, later stage of disease, and higher percentage of large tumors. Patients with >30% postvaccination MCP-1 increase also showed significant increases in E75-specific CD8(+) T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination. CONCLUSIONS: High serum MCP-1 levels in breast cancer patients correlate with favorable prognostic variables and increased preexisting /neu immunity. E75 vaccination induces the largest MCP-1 response in patients with unfavorable clinicopathologic variables. Therefore, low serum MCP-1 levels may identify patients with worse prognosis and those most likely to benefit from this vaccination.

Adult↗
PubMed2006

Vaccination with a HER2/neu peptide induces intra- and inter-antigenic epitope spreading in patients with early stage breast cancer.

BACKGROUND: We are conducting clinical vaccine trials with the HER2/neu peptide, E75, in patients with breast cancer. The purpose of this study was to demonstrate clonal expansion of E75-specific CD8(+) T cells and to identify intra- and interantigenic epitope spreading. METHOD: Pre- and postvaccination peripheral blood leukocyte samples (24 node positive [NP] and 20 node negative [NN]) from 44 vaccinated patients were analyzed. HLA-A2:Ig dimer molecules were loaded with the HER2 peptides, E75 or GP2, and were used with anti-TcR and CD8 antibodies to stain peripheral blood leukocyte immediately ex vivo and were analyzed with flow cytometry. In 8 randomly selected patients, dimers were loaded with the folate binding protein peptide E41 to evaluate for interantigenic epitope spreading. RESULTS: All patients with NP and 95% of the patients with NN showed E75-specific clonal expansion. Patients with NN showed more robust expansion. All patients with NP and 85% of the patients with NN showed evidence of intra-antigenic epitope that was spreading to GP2. However, patients with NN showed only moderate expansion to this subdominant epitope, which was not included in the immunizing mix. The degree of HER2/neu expression and disease stage impacted the ability to expand clonally E75- and GP2-specific CD8(+) T cells. Evidence of interantigenic epitope spreading to E41 was shown in 63% of the patients who were tested. CONCLUSION: Our data provide evidence for the induction of intra- and interantigenic epitope spreading that results from a single HER2/neu peptide vaccine even in early staged patients. The ability to raise immunity to multiple tumor antigens depends on both the degree of HER2/neu expression and the extent of disease. Epitope spreading is an essential element for the success of a peptide vaccine strategy.

Antigens, Neoplasm↗
PubMed2006

A novel device developed, tested, and used for warming and maintaining intravenous fluids in a forward surgical team during Operation Enduring Freedom.

OBJECTIVE: To determine whether an accessory to the Bair Hugger warming unit (BHWU), a piece of equipment intrinsic to the forward surgical team, could be designed and used to warm and to maintain large volumes of intravenous fluids at an optimal infusion temperature in an austere environment. METHODS: The X-1 is a simple, collapsible, 5-gallon nylon cooler with handles, modified with a port for the BHWU hose and a one-way flutter valve vent. RESULTS: The warming of intravenous fluids to the optimal infusion temperature was accomplished with the BHWU and X-1. The warming time was influenced by the ambient temperature, the starting temperature of the fluids, and the number of bags being warmed. The warmed fluid could be stored and maintained in the X-1. The heat retention of the fluids was influenced by the ambient temperature, the number of bags warmed, and the insulating properties of the X-1. CONCLUSIONS: The BHWU can be used with the compact X-1 to warm and to store large volumes of intravenous fluids at the optimal infusion temperature in the field environment and was successfully used by a forward surgical team in Afghanistan, during Operation Enduring Freedom, for the treatment of combat-wounded soldiers.

Afghanistan↗
PubMed2005

Phase I clinical trial of a HER-2/neu peptide (E75) vaccine for the prevention of prostate-specific antigen recurrence in high-risk prostate cancer patients.

PURPOSE: The E75 peptide is an immunogenic peptide from the HER-2/neu protein that is substantially expressed in prostate cancer. We are conducting a clinical trial of an E75/granulocyte macrophage colony-stimulating factor vaccine to prevent post-prostatectomy prostate-specific antigen (PSA) recurrences in high-risk prostate cancer (HRPC) patients. EXPERIMENTAL DESIGN: Prostate cancer patients at high risk for recurrence were prospectively evaluated and identified by the validated Center for Prostate Disease Research (CPDR)/CaPSURE high-risk equation. From these high-risk equation patients, 27 HER-2/neu-expressing prostate cancer patients were enrolled. HLA-A2+ patients (n = 17) were vaccinated, whereas HLA-A2- patients (n = 10) were followed as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence were measured. RESULTS: This vaccine is safe with only minor toxicities observed. Additionally, the vaccine is immunogenic with all patients showing both in vivo and in vitro phenotypic and functional immune responses, although variable. HLA-A2+ patients were found to have larger tumors, higher postoperative Gleason scores, and more high-risk CPDR scores than HLA-A2- patients. Despite these differences, disease-free survival was not different between the vaccinated HLA-A2+ patients and the HLA-A2- controls at a median follow up of 23 months. Three of the four vaccinated patients that recurred had rising PSAs at the initiation of the trial. Ex vivo phenotypic assays were predictive of recurrences and correlated in general with functional assays. CONCLUSIONS: The E75 vaccine strategy is safe and effective in eliciting an immune response against the HER-2/neu protein in HRPC patients and may be useful as a preventive strategy against disease recurrence. Vaccination in response to a rising PSA may be too late.

Aged↗
PubMed2005

Clinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patients.

PURPOSE: E75 is an immunogenic peptide from the HER2/neu protein that is highly expressed in breast cancer. We are conducting a clinical trial of an E75 + granulocyte-macrophage colony-stimulating factor vaccine to assess safety, immunologic response, and the prevention of clinical recurrences in patients with disease-free, node-positive breast cancer (NPBC). PATIENTS AND METHODS: Fifty-three patients with NPBC were enrolled and HLA typed. HLA-A2+ patients (n = 24) were vaccinated, and HLA-A2- patients (n = 29) are observed prospectively as clinical controls. Local/systemic toxicities, immunologic responses, and time to recurrence are being measured. RESULTS: Only minor toxicities have occurred (one grade 3 [4%]). All patients have demonstrated clonal expansion of E75-specific CD8+T cells that lysed HER2/neu-expressing tumor cells. An optimal dosage and schedule have been established. Patients have developed delayed-type hypersensitivity reactions to E75 postvaccination compared with controls (33 v 7 mm; P < .01). HLA-A2+ patients have been found to have larger, more poorly differentiated, and more hormonally insensitive tumors compared to HLA-A2- patients. Despite this, the only two deaths have occurred in the control group. The disease-free survival in the vaccinated group is 85.7% compared to 59.8% in the controls at 22 months' median follow-up with a recurrence rate of 8% compared to 21%, respectively (P < .19). Median time to recurrence in the vaccinated patients was prolonged (11 v 8 months), and recurrence correlated with a weak delayed-type hypersensitivity response. CONCLUSION: This HER2/neu (E75) vaccine is safe and effective in eliciting a peptide-specific immune response in vivo. Induced HER2/neu immunity seems to reduce the recurrence rate in patients with NPBC.

Adult↗
PubMed2005

Sensitivity of undifferentiated, high-TCR density CD8+ cells to methylene groups appended to tumor antigen determines their differentiation or death.

CD8(+) cells expressing high numbers of TCR per cell (TCR(hi)) are considered important mediators of antitumor effects. To understand the relationship between TCR density and antigen affinity for TCR in the outcome of stimulation with antigen and differentiation of CTL recognizing tumor antigen, we analyzed perforin induction in ovarian tumor-associated lymphocytes in response to the smallest possible changes in the atomic forces of interaction between antigen and TCR. Stimulating undifferentiated, apoptosis-resistant CD8(+) cells expressing high levels of E75-TCR (TCR(hi)) with variants of the CTL epitope E75, HER-2 (369-377), induced their stepwise differentiation, first to IFN-gamma(+) Perf(-) and to TCR(hi) IFN-gamma(+) Perf(+) cells. Blocking caspase-9 activation at antigen stimulation also enhanced the generation of TCR(hi) Perf(hi) cells, demonstrating that TCR density dictated the pathway of death activated by stimulation with the same agonist. Expansion and differentiation of TCR(hi) Perf(+) CTL required an agonist of optimal CH(2) side chain length, which in this study was equal to two CH(2) groups appended to E75 at the Gly(4) position. Side chains one CH(2) shorter or longer than optimal were either less stimulatory or induced death of TCR(hi) Perf(+) cells. Differentiation of TCR(hi) CD8(+) cells can be finely tuned by synthetic amino acids in the peptide, whose side chains induce small increments in the affinity of the antigen for TCR below the affinity which induce apoptosis.

Antigens, Neoplasm↗
PubMed2005

Electrical impedance scanning of thyroid nodules before thyroid surgery: a prospective study.

BACKGROUND: Electrical impedance scanning (EIS) is a novel imaging technique based on differential electrical conductivity and capacitance of malignant and normal human tissues. The aim of this study was to evaluate the accuracy of EIS in the detection of thyroid malignancies. METHODS: Patients with thyroid nodules scheduled for thyroid surgery were eligible for the study. Enrolled patients underwent EIS with a T-Scan 2000ED. Nodule location, size, and type (cystic vs. solid) measured by ultrasound, cytology results, thyroid conductivity, and capacitance calculated by EIS were recorded. EIS results were interpreted as positive or negative for malignancy and compared with final histopathology results. Study end points included EIS accuracy, sensitivity, specificity, negative and positive predictive values, and false-positive and false-negative rates. RESULTS: Sixty-four patients were enrolled onto the study, and all underwent either lobectomy-isthmusectomy (20%) or total thyroidectomy (80%). The mean tumor diameter was 2.64 +/- 14.8 mm. Thyroid cancers were identified by histology in 30 patients (46.9%). There were 11 false-positive and four false-negative cases. The overall diagnostic accuracy of EIS was 76.6% (49 of 64 correct diagnoses). The sensitivity and specificity of EIS were 86.7% (26 of 30 true positive) and 67.6% (23 of 34 true negative), respectively. The corresponding positive and negative predictive values were 70.3% and 85.2%. CONCLUSIONS: EIS is a potentially useful imaging modality for differentiating thyroid neoplasms. If these results are confirmed in large-scale trials, EIS may be an important part of the evaluation of thyroid nodules.

Adolescent↗
PubMed2005

Evaluation of the CD107 cytotoxicity assay for the detection of cytolytic CD8+ cells recognizing HER2/neu vaccine peptides.

The recently reported FACS-based CD107 assay has been used in human HIV and CMV antigen models as well as in the ex vivo analysis of tumor cytolytic T cells in a melanoma model by a single group. The purpose of our study was to validate this assay and to use it in previously untested viral and tumor antigen models. Specifically, we investigated the use of the novel CD107 cytotoxicity assay in the detection of influenza and HER2/neu tumor-specific cytolytic CD8+ T cells. CD8+ T cells from HLA-A2+ healthy donors were stimulated with autologous dendritic cells pulsed with FluM or the HER2/neu peptides, E75 or GP2. These CD8+ T cells were then tested in cytotoxicity assays at varying effector:target (E:T) ratios against T2 targets. Cytotoxicity was measured by detection of CD107a and b on the surface of CD8+ T cells. An E:T of 1:5 was found to optimize the resulting percentage of CD8+CD107+ T cells. E75- and GP2-stimulated CD8+ T cells were then tested in cytotoxicity assays with MCF-7 (HER2/neu+HLA-A2+) and AU565 (HER2/neu+HLA-A2-) tumor cells. Cytotoxicity was measured by both the CD107 assay and the (51)Cr release assay. Results of cytotoxicity were then correlated between these two assays. In representative experiments, the CD107 assay identified average specific increases for E75- and GP2-stimulated cells of 4.26 and 3.57%, respectively. These results correlated favorably with cytotoxicity as measured by the traditional (51)Cr assay. These findings confirm preliminary reports of the CD107 assay and suggest its usefulness for monitoring cancer trials.

Antigens, CD↗
PubMed2005

The most frequently requested precombat refresher training by the Special Forces medics during Operation Enduring Freedom.

The tactical environment and the mission given the Special Operations Forces in Afghanistan during the initial phases of Operation Enduring Freedom placed the Special Operations Forces medics (18Ds) in a position of significant medical responsibility. The 18Ds became the primary care providers for the indigenous anti-Taliban fighters as well as U.S. military personnel; the care of the latter was further complicated by long evacuation times. Because of these issues and several events that occurred in the combat zone, the 18Ds requested their supporting forward surgical team (FST) (274th FST) to provide specific refresher training before combat deployment into Afghanistan. The areas of greatest interest and concern were orthopedics, field transfusions, and field-expedient anesthesia. It is hoped that the training prepared and given to the 18Ds by the personnel of the 274th FST and presented in this article not only was useful to them but also will be of benefit to 18Ds who find themselves in similar situations in the future.

Afghanistan↗
PubMed2005

The 274th Forward Surgical Team experience during Operation Enduring Freedom.

The 274th Forward Surgical Team (FST) was deployed in support of Operation Enduring Freedom from October 14, 2001 to May 8, 2002. During this period, the FST was asked to perform many nondoctrinal missions. The FST was tasked with functioning as a mini-combat support hospital during the earlier phases of Operation Enduring Freedom, performing in-flight surgical procedures and resuscitation of combat wounded, conducting split operations with surgical coverage of both Karshi and Khanabad, Uzbekistan, and Bagram, Afghanistan, and leading the multinational medical coalition assembled for Operation Anaconda and other combat operations staged from Bagram. Overall, the 274th FST took care of approximately 90% of U.S. combat casualties during this period and treated a total of 221 combat casualties. The FST treated 103 total surgical cases, including 73 with combat wounds. At the time, this experience with combat casualties and the surgical care of combat wounds was the largest since the Persian Gulf War. More importantly, this account describes the flow, frequency, and type of combat casualties seen in a low-intensity conflict like that being waged currently in Afghanistan. It is hoped that this depiction will aid in the preparation, equipping, and overall utilization of surgical assets in similar future conflicts.

Afghanistan↗
PubMed2005

Combat casualties in Afghanistan cared for by a single Forward Surgical Team during the initial phases of Operation Enduring Freedom.

BACKGROUND: The 274th Forward Surgical Team (FST) was the first FST deployed to Bagram, Afghanistan, to provide surgical care for combat casualties during the initial phases of Operation Enduring Freedom. This is an analysis of the distribution, cause, and severity of wounds for combat casualties and the surgical procedures they required. METHODS: A prospective database was maintained for combat casualties cared for by the 274th FST. The database included demographic data, vital status, mechanism of injury, distribution and severity of wounds, and surgical care provided. RESULTS: The FST cared for 224 combat casualties, including 153 U.S. soldiers, 19 coalition soldiers, 32 Afghan militia forces soldiers, and 20 detainees. Fragments were the most common mechanism of injury (49%), and the extremity was the most common location of injury (58%), whereas gunshot wounds were the most common cause of death (57%). There were few significant head, chest, or abdominal wounds (13%). The FST treated 103 surgical cases (73 with combat wounds), including neurosurgical, thoracic, general, orthopedic, and vascular cases, with a total of 180 procedures. CONCLUSIONS: The distribution, cause, and severity of wounds were similar to those in the Persian Gulf War, despite the obvious differences between these conflicts. The use of modern technologies, such as compact, portable, ultrasound and digital X-ray systems, expanded the capabilities of the FST. Even low-intensity conflicts can produce significant numbers of combat casualties, and the FST must be manned, trained, equipped, and supplied to treat a wide variety of combat wounds.

Afghanistan↗
PubMed2004

Direct measurement of peptide-specific CD8+ T cells using HLA-A2:Ig dimer for monitoring the in vivo immune response to a HER2/neu vaccine in breast and prostate cancer patients.

HER2/neu is a proto-oncogene and a member of the epidermal growth factor receptor family of proteins that is overexpressed in numerous types of human cancer. We are currently conducting clinical trials with the HER2/neu E75 peptide vaccine in breast and prostate cancer patients. We have evaluated the use of HLA-A2 dimer molecule for the immunological monitoring of cancer patients receiving the E75 peptide vaccine. Peripheral blood samples from patients receiving the vaccine were stained with HLA-A2 dimers containing the vaccine peptide E75 or control peptides and analyzed by flow cytometry. We compared the HLA-A2 dimer assay to standard methods of immunologic monitoring (IFN-gamma release, lymphocyte proliferation, and cytotoxicity). The HLA-A2 dimer assay was also compared with the HLA-A2 tetramer assay. E75 peptide-specific CD8 T cells were detected directly in the peripheral blood of patients by staining with E75-HLA-A2 dimers and CD8 antibodies. T cell cultures generated by repeated stimulations using E75 peptide-pulsed dendritic cells showed increased staining with E75-peptide loaded HLA-A2 dimers. Simultaneously analysis by the dimer assay and standard immunologic assays demonstrated that the dimer-staining assay correlated well with these methods of immunologic monitoring. A direct comparison using E75-specific HLA-A2 tetramers and HLA-A2 dimers for the detection of E75-specific CD8 T cells in peripheral blood showed comparable results with the two assays. Our findings indicate that the HLA-A2 dimer is a powerful new tool for directly quantifying and monitoring immune responses of antigen-specific T cells in peptide vaccine clinical trials.

Antibody Formation↗