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Biomedical subjects

Marc Berger

Publications and source records attributed to Marc Berger.

8 recordsLinked to original sources
PubMed2006

Human antibodies for immunotherapy development generated via a human B cell hybridoma technology.

Current strategies for the production of therapeutic mAbs include the use of mammalian cell systems to recombinantly produce Abs derived from mice bearing human Ig transgenes, humanization of rodent Abs, or phage libraries. Generation of hybridomas secreting human mAbs has been previously reported; however, this approach has not been fully exploited for immunotherapy development. We previously reported the use of transient regulation of cellular DNA mismatch repair processes to enhance traits (e.g., affinity and titers) of mAb-producing cell lines, including hybridomas. We reasoned that this process, named morphogenics, could be used to improve suboptimal hybridoma cells generated by means of ex vivo immunization and immortalization of antigen-specific human B cells for therapeutic Ab development. Here we present a platform process that combines hybridoma and morphogenics technologies for the generation of fully human mAbs specific for disease-associated human antigens. We were able to generate hybridoma lines secreting mAbs with high binding specificity and biological activity. One mAb with strong neutralizing activity against human granulocyte-macrophage colony-stimulating factor was identified that is now considered for preclinical development for autoimmune disease indications. Moreover, these hybridoma cells have proven suitable for genetic optimization using the morphogenics process and have shown potential for large-scale manufacturing.

Amino Acid Sequence↗
PubMed2006

Do drug formulary policies reflect evidence of value?

OBJECTIVE: To investigate the extent to which preferred drug lists and tiered formularies reflect evidence of value, as measured in published cost-utility analyses (CUAs). METHODS: Using 1998-2001 data from a large registry of cost-effectiveness analyses, we examined the 2004 Florida Medicaid preferred drug list and the 2004 Harvard Pilgrim Pharmacy Program 3-tier formulary, and compared cost-utility ratios (standardized to 2002 US dollars) of drugs with preferred and nonpreferred status. RESULTS: Few drugs on the formularies had any cost-utility data available. Of those that did, median cost-utility ratios were somewhat higher (less favorable) for Florida's preferred drugs compared with the nonpreferred drugs (25,465 dollars vs 13,085 dollars; P = .09). Ratios did not differ for drugs on tiers 1 and 2 of the Harvard Pilgrim formulary, although they were higher for tier 3 and for excluded drugs (18,309 dollars, 18,846 dollars, 52,119 dollars, and 22,580 dollars, respectively; P = .01). Among therapies reported to be cost-saving or to have cost-utility ratios below 50,000 dollars, 77% had favored status in Florida Medicaid and 73% in Harvard Pilgrim. Among dominated drug interventions (reported to be more costly and less effective than alternatives), 95% had favored status in Florida Medicaid and 56% in Harvard Pilgrim. CONCLUSIONS: This study underscores the paucity of published cost-utility data available to formulary committees. Some discrepancies prevail between the value of drugs, as reflected in published cost-utility ratios, and the formulary placement policies of 2 large health plans.

Boston↗
PubMed2005

Radiotherapy of human xenograft NSCLC tumors in nude mice with a 90Y-labeled anti-tissue factor antibody.

Tissue factor (TF) is a type I transmembrane protein and the initiator of the extrinsic blood coagulation pathway. TF plays a critical role in tumor development and its overexpression is observed in many tumors. To understand the prevalence and relative level of TF expression in non-small-cell lung cancer (NSCLC), we analyzed 50 NSCLC tumors by immunohistochemical staining and found that 88% of human NSCLC tumors overexpressed TF. We then generated a high affinity anti-TF antibody, TF278, which specifically binds TF on the surface of cells and is internalized upon binding. An 111In-labeled TF278 demonstrated favorable tumor accumulation in an SW-900 xenograft tumor model with a maximum mean percent of injected dose per gram of tissue (%ID/g) of 73.1% at 96 hours postinjection. In addition, we labeled the antibody with 90Y and tested its ability to inhibit the growth of tumors in an SW-900 xenograft tumor model in immunocompromised mice. The 90Y-TF278 slowed the growth of SW-900 tumors at a 50 microCi dose and completely regressed SW-900 tumors at a 150 microCi dose with little toxicity.

Animals↗
PubMed2004

When does quality-adjusting life-years matter in cost-effectiveness analysis?

PURPOSE: This paper investigates the impact of quality-of-life adjustment on cost-effectiveness analyses, by comparing ratios from published studies that have reported both incremental costs per (unadjusted) life-year and per quality-adjusted life-year for the same intervention. METHODS: A systematic literature search identified 228 original cost-utility analyses published prior to 1998. Sixty-three of these analyses (173 ratio pairs) reported both cost/LY and cost/QALY ratios for the same intervention, from which we calculated medians and means, the difference between ratios (cost/LY minus cost/QALY) and between reciprocals of the ratios, and cost/LY as a percentage of the corresponding cost/QALY ratio. We also compared the ratios using rank-order correlation, and assessed the frequency with which quality-adjustment resulted in a ratio crossing the widely used cost-effectiveness thresholds of 20, 000 US dollars, 50,000 US dollars, and 100,000 US dollars/QALY or LY. RESULTS: The mean ratios were 69,100 US dollars/LY and 103,100 US dollars/QALY, with corresponding medians of 24,600 US dollars/LY and 20,400 US dollars/QALY. The mean difference between ratios was approximately -34,300 US dollars (median difference: 1300 US dollars), with 60% of ratio pairs differing by 10,000 US dollars/year or less. Mean difference between reciprocals was 59 (QA)LYs per million dollars (median: 2.1). The Spearman rank-order correlation between ratio types was 0.86 (p<0.001). Quality-adjustment led to a ratio moving either above or below 50,000 US dollars/LY (or QALY) in 8% of ratio pairs, and across 100,000 US dollars in 6% of cases. CONCLUSIONS: In a sizable fraction of cost-utility analyses, quality adjusting did not substantially alter the estimated cost-effectiveness of an intervention, suggesting that sensitivity analyses using ad hoc adjustments or 'off-the-shelf' utility weights may be sufficient for many analyses. The collection of preference weight data should be subjected to the same scrutiny as other data inputs to cost-effectiveness analyses, and should only be under-taken if the value of this information is likely to be greater than the cost of obtaining it.

Cost-Benefit Analysis↗
PubMed2002

Association of asthma control with health care utilization: a prospective evaluation.

Population-based disease management should be enhanced by good risk assessment models and instruments. We prospectively evaluated the ability of a simple measure of short-term asthma control (scored 0 to 4) to predict asthma 12-mo health care utilization (HCU). A total of 5,172 adult asthma patients completed a brief questionnaire in fall 1997 to assess current level of asthma control. We then evaluated HCU for calendar year 1998. Ninety-three percent had health plan eligibility in 1998 and were included in this analysis. Both acute and routine asthma utilization increased with increasing numbers of asthma control problems. Rates of acute care episodes were 3.5 (95% confidence interval [CI] = 2.9, 4.3) times more likely for those with 3 to 4 control problems versus those with no control problems. Lesser, but statistically significant, increases were seen for those with two (relative risk [RR] = 1.7, 95% CI = 1.4, 2.2) or one (RR = 1.4, 95% CI = 1.1, 1.8) control problems. These patterns were similar for men and women, and diminished with increasing age. The asthma control index contributed significantly to prospective prediction models even after adjusting for administrative data such as medication use and prior HCU. These data reinforce the usefulness of measures of short-term asthma control both for the individual clinician and for those interested in population-based asthma management.

Adolescent↗
PubMed2002

Successful extracorporeal photochemotherapy for chronic graft-versus-host disease in pediatric patients.

A total of 254 extracorporeal photochemotherapy (ECP) procedures were performed in 8 children (median age 10 years; range 5-15) with extensive resistant chronic graft-versus-host disease (GVHD). ECP was carried out in the pediatric environment using a Cobe Spectra separator and UV-MATIC irradiator. A peripheral venous with a single-lumen permanent central catheter access (69% of ECP-apheresis) or a dual-lumen permanent central catheter access (26% of ECP-apheresis) were used preferentially. A median platelet decrease of 17% (0-71) (p = 0.0001) and median hemoglobin level decrease of 15 g/L (0-31)(p = 0.0001) were noted following each ECP-apheresis. However, none of the patients had profound thrombocytopenia or anemia. Two minor episodes of catheter related-bacteriemia (Staphylococcus aureus) were noted (2310 catheter-days). A negative correlation was found between lymphocyte collection efficacy (median = 38%) and pre ECP-apheresis lymphocyte count (r = 0.4, p = 0.00001). The median of 5 x 10(7) lymphocytes/kg (0.1-50.10(7)/kg) was irradiated in each procedure. All patients are alive and well, and 7/8 experienced a dramatic improvement in their cutaneous status. Liver and gut disease resolved completely in 4/6 and 5/5 patients, respectively. In all patients, a concomitant immunosuppressive therapy was stopped (5/8) or considerably reduced (3/8). Five patients with more than 2 years follow-up after discontinuation of ECP are in remission with no immunosuppression treatment. They have normal growth rates and normal school and sport activity. Our study shows that ECP is beneficial, well tolerated, and can be safely used for chronic GVHD treatment even in young children with low body weight and a poor performance status. We believe that having a dedicated pediatric environment together with an experienced, motivated, and specifically pediatric team is of crucial importance for improving patient's acceptance of this long-term therapeutic program.

Adolescent↗